Exceptional stratospheric contribution to human fingerprints on atmospheric temperature.

In 1967, scientists used a simple climate model to predict that human-caused increases in atmospheric CO2 should warm Earth's troposphere and cool the stratosphere. This important signature of anthropogenic climate change has been documented in weather balloon and satellite temperature measurements extending from near-surface to the lower stratosphere. Stratospheric cooling has also been confirmed in the mid to upper stratosphere, a layer extending from roughly 25 to 50 km above the Earth's surface (S25 - 50). To date, however, S25 - 50 temperatures have not been used in pattern-based attribution studies of anthropogenic climate change. Here, we perform such a "fingerprint" study with satellite-derived patterns of temperature change that extend from the lower troposphere to the upper stratosphere. Including S25 - 50 information increases signal-to-noise ratios by a factor of five, markedly enhancing fingerprint detectability. Key features of this global-scale human fingerprint include stratospheric cooling and tropospheric warming at all latitudes, with stratospheric cooling amplifying with height. In contrast, the dominant modes of internal variability in S25 - 50 have smaller-scale temperature changes and lack uniform sign. These pronounced spatial differences between S25 - 50 signal and noise patterns are accompanied by large cooling of S25 - 50 (1 to 2[Formula: see text]C over 1986 to 2022) and low S25 - 50 noise levels. Our results explain why extending "vertical fingerprinting" to the mid to upper stratosphere yields incontrovertible evidence of human effects on the thermal structure of Earth's atmosphere.

Stabilization of RRBP1 mRNA via an m6A-dependent manner in prostate cancer constitutes a therapeutic vulnerability amenable to small-peptide inhibition of METTL3.

Mounting evidence has implicated the RNA m6A methylation catalyzed by METTL3 in a wide range of physiological and pathological processes, including tumorigenesis. The detailed m6A landscape and molecular mechanism of METTL3 in prostate cancer (PCa) remains ill-defined. We find that METTL3 is overexpressed in PCa and correlates with worse patient survival. Functional studies establish METTL3 as an oncoprotein dependent on its m6A enzymatic activity in both AR+ and AR- PCa cells. To dissect the regulatory network of m6A pathway in PCa, we map the m6A landscape in clinical tumor samples using m6A-seq and identify genome-wide METTL3-binding transcripts via RIP-seq. Mechanistically, we discover RRBP1 as a direct METTL3 target in which METTL3 stabilizes RRBP1 mRNA in an m6A-dependent manner. RRBP1 positively correlates with METTL3 expression in PCa cohorts and exerts an oncogenic role in aggressive PCa cells. Leveraging the 3D structural protein-protein interaction between METTL3 and METTL14, we successfully develop two potential METTL3 peptide inhibitors (RM3 and RSM3) that effectively suppress cancer cell proliferation in vitro and tumor growth in vivo. Collectively, our study reveals a novel METTL3/m6A/RRBP1 axis in enhancing aggressive traits of PCa, which can be therapeutically targeted by small-peptide METTL3 antagonists.

A multitiered haplotype strategy to enhance phased assembly and fine mapping of a disease resistance locus.

Fine mapping of quantitative trait loci (QTL) to dissect the genetic basis of traits of interest is essential to modern breeding practice. Here, we employed a multitiered haplotypic marker system to increase fine mapping accuracy by constructing a chromosome-level, haplotype-resolved parental genome, accurate detection of recombination sites, and allele-specific characterization of the transcriptome. In the first tier of this system, we applied the preexisting panel of 2,000 rhAmpSeq core genome markers that is transferable across the entire Vitis genus and provides a genomic resolution of 200 kb to 1 Mb. The second tier consisted of high-density haplotypic markers generated from Illumina skim sequencing data for samples enriched for relevant recombinations, increasing the potential resolution to hundreds of base pairs. We used this approach to dissect a novel Resistance to Plasmopara viticola-33 (RPV33) locus conferring resistance to grapevine downy mildew, narrowing the candidate region to only 0.46 Mb. In the third tier, we used allele-specific RNA-seq analysis to identify a cluster of 3 putative disease resistance RPP13-like protein 2 genes located tandemly in a nonsyntenic insertion as candidates for the disease resistance trait. In addition, combining the rhAmpSeq core genome haplotype markers and skim sequencing-derived high-density haplotype markers enabled chromosomal-level scaffolding and phasing of the grape Vitis × doaniana 'PI 588149' assembly, initially built solely from Pacific Biosciences (PacBio) high-fidelity (HiFi) reads, leading to the correction of 16 large-scale phasing errors. Our mapping strategy integrates high-density, phased genetic information with individual reference genomes to pinpoint the genetic basis of QTLs and will likely be widely adopted in highly heterozygous species.

Impact of crosslinking agents with steric cyclic groups on the properties of polymer-dispersed liquid crystals.

As a type of intelligent dimming film, polymer-dispersed liquid crystals (PDLCs) have been widely applied in various fields, such as smart windows, light shutters and displays. The properties of PDLCs are greatly influenced by the structure of the raw materials. In this work, the impact of crosslinking agents with different cyclic or chain groups was investigated by comparing the electro-optical performance and the morphology of the polymer matrix in the as-made PDLC films. It was found that the incorporation of large steric groups into the crosslinking agents can alter the morphology of the polymer matrix and thus affect the electro-optical properties. However, the impact is distinct when the spatial structure or rigidity is different. Besides, a combination of crosslinking agents with flexible alkyl-chain structures and steric structures can further reduce the threshold voltage while keeping the high contrast ratio. After detailed comparison, an optimized combination of BDDA/TCDDA in a weight ratio of 1/1 is selected to demonstrate the enhanced properties of the as-constructed film with a thickness of 20 µm. It exhibits low threshold voltage (8.2 V), low saturation voltage (21.2 V) and a high contrast ratio (203) simultaneously. This research offers an optimizing method from the crosslinking agent perspective and is anticipated to promote the further improvement of the PDLC's performance.

Mitral valvuloplasty using real-time three-dimensional transesophageal echocardiography.

OBJECTIVE: This study aimed to investigate the structure of the mitral valve in patients undergoing mitral valvuloplasty (MVP) using real-time three-dimensional transesophageal echocardiography (RT-3D-TEE). The main objective was to study the relationship between intraoperative annuloplasty ring size and mitral valve structure dimensions, with a focus on exploring the application value of RT-3D-TEE in MVP. METHODS: A total of 28 patients with degenerative mitral regurgitation (DMR), who underwent MVP between February and September 2022, as well as 12 normal control cases, were enrolled in this study. The MV annulus and leaflets were quantitatively analyzed using MVN software. RESULTS: The DMR group exhibited significantly greater dimensions in various parameters of the mitral valve, including the anterolateral-to-posteromedial diameter (DAlPm ), anterior-to-posterior diameter (DAP ), annulus height (HA ), three-dimensional annulus circumference (CA3D ), two-dimensional annulus area (AA2D ), anterior leaflet area (Aant ), posterior leaflet area (Apost ), anterior leaflet length (Lant ), posterior leaflet length (Lpost ), and tenting volume (Vtent ) compared to the control group. CONCLUSION: Real-time three-dimensional transesophageal echocardiography provides valuable insights into the morphological structure of the mitral valve and lesion location. It can aid in surgical decision-making, validate the success of MVP, and potentially reduce mortality and complications associated with mitral valve repair procedures.

TOR functions as a molecular switch connecting an iron cue with host innate defense against bacterial infection.

As both host and pathogen require iron for survival, iron is an important regulator of host-pathogen interactions. However, the molecular mechanism by which how the availability of iron modulates host innate immunity against bacterial infections remains largely unknown. Using the metazoan Caenorhabditis elegans as a model, we demonstrate that infection with a pathogenic bacterium Salmonella enterica serovar Typhimurium induces autophagy by inactivating the target of rapamycin (TOR). Although the transcripts of ftn-1 and ftn-2 encoding two H-ferritin subunits are upregulated upon S. Typhimurium infection, the ferritin protein is kept at a low level due to its degradation mediated by autophagy. Autophagy, but not ferritin, is required for defense against S. Typhimurium infection under normal circumstances. Increased abundance of iron suppresses autophagy by activating TOR, leading to an increase in the ferritin protein level. Iron sequestration, but not autophagy, becomes pivotal to protect the host from S. Typhimurium infection in the presence of exogenous iron. Our results show that TOR acts as a regulator linking iron availability with host defense against bacterial infection.

Multiple independent recombinations led to hermaphroditism in grapevine.

Hermaphroditic (perfect) flowers were a key trait in grapevine domestication, enabling a drastic increase in yields due to the efficiency of self-pollination in the domesticated grapevine (Vitis vinifera L. ssp. vinifera). In contrast, all extant wild Vitis species are dioecious, each plant having only male or female flowers. In this study, we identified the male (M) and female (f) haplotypes of the sex-determining region (SDR) in the wild grapevine species V. cinerea and confirmed the boundaries of the SDR. We also demonstrated that the SDR and its boundaries are precisely conserved across the Vitis genus using shotgun resequencing data of 556 wild and domesticated accessions from North America, East Asia, and Europe. A high linkage disequilibrium was found at the SDR in all wild grape species, while different recombination signatures were observed along the hermaphrodite (H) haplotype of 363 cultivated accessions, revealing two distinct H haplotypes, named H1 and H2. To further examine the H2 haplotype, we sequenced the genome of two grapevine cultivars, 'Riesling' and 'Chardonnay'. By reconstructing the first two H2 haplotypes, we estimated the divergence time between H1 and H2 haplotypes at ∼6 million years ago, which predates the domestication of grapevine (∼8,000 y ago). Our findings emphasize the important role of recombination suppression in maintaining dioecy in wild grape species and lend additional support to the hypothesis that at least two independent recombination events led to the reversion to hermaphroditism in grapevine.

20(R)-ginsenoside Rg3 attenuates cerebral ischemia-reperfusion injury by mitigating mitochondrial oxidative stress via the Nrf2/HO-1 signaling pathway.

Reducing mitochondrial oxidative stress has become an important strategy to prevent neuronal death in ischemic stroke. Previous studies have shown that 20(R)-ginsenoside Rg3 can significantly improve behavioral abnormalities, reduce infarct size, and decrease the number of apoptotic neurons in cerebral ischemia/reperfusion injury rats. However, it remains unclear whether 20(R)-ginsenoside Rg3 can inhibit mitochondrial oxidative stress in ischemic stroke and the potential molecular mechanism. In this study, we found that 20(R)-ginsenoside Rg3 notably inhibited mitochondrial oxidative stress in middle cerebral artery occlusion/reperfusion (MCAO/R) rats and maintained the stability of mitochondrial structure and function. Treatment with 20(R)-ginsenoside Rg3 also decreased the levels of mitochondrial fission proteins (Drp1 and Fis1) and increased the levels of fusion proteins (Opa1, Mfn1, and Mfn2) in MCAO/R rats. Furthermore, we found that 20(R)-ginsenoside Rg3 promoted nuclear aggregation of nuclear factor erythroid2-related factor 2 (Nrf2) but did not affect Kelch-like ECH-associated protein-1 (Keap1), resulting in the downstream expression of antioxidants. In in vitro oxygen-glucose deprivation/reperfusion stroke models, the results of PC12 cells treated with 20(R)-ginsenoside Rg3 were consistent with animal experiments. After transfection with Nrf2 short interfering RNA (siRNA), the protective effect of 20(R)-ginsenoside Rg3 on PC12 cells was reversed. In conclusion, the inhibition of mitochondrial oxidative stress plays a vital position in the anti-cerebral ischemia-reperfusion injury of 20(R)-ginsenoside Rg3, and its neuroprotective mechanism is related to the activation of the nuclear factor erythroid2-related factor 2/heme oxygenase 1 signaling pathway.

Photoelectric H2S Sensing Based on Electrospun Hollow CuO-SnO2 Nanotubes at Room Temperature.

Pure tin oxide (SnO2) as a typical conductometric hydrogen sulfide (H2S) gas-sensing material always suffers from limited sensitivity, elevated operation temperature, and poor selectivity. To overcome these hindrances, in this work, hollow CuO-SnO2 nanotubes were successfully electrospun for room-temperature (25 °C) trace H2S detection under blue light activation. Among all SnO2-based candidates, a pure SnO2 sensor showed no signal, even toward 10 ppm, while the 1% CuO-SnO2 sensor achieved a limit of detection (LoD) value of 2.5 ppm, a large response of 4.7, and a short response/recovery time of 21/61 s toward 10 ppm H2S, as well as nice repeatability, long-term stability, and selectivity. This excellent performance could be ascribed to the one-dimensional (1D) hollow nanostructure, abundant p-n heterojunctions, and the photoelectric effect of the CuO-SnO2 nanotubes. The proposed design strategies cater to the demanding requirements of high sensitivity and low power consumption in future application scenarios such as Internet of Things and smart optoelectronic systems.

Survival and infectivity of second-stage root-knot nematode Meloidogyne incognita juveniles depend on lysosome-mediated lipolysis.

Adaptation to nutrient deprivation depends on the activation of metabolic programs to use reserves of energy. When outside a host plant, second-stage juveniles (J2) of the root-knot nematode (Meloidogyne spp.), an important group of pests responsible for severe losses in the production of crops (e.g., rice, wheat, and tomato), are unable to acquire food. Although lipid hydrolysis has been observed in J2 nematodes, its role in fitness and the underlying mechanisms remain unknown. Using RNA-seq analysis, here, we demonstrated that in the absence of host plants, the pathway for the biosynthesis of polyunsaturated fatty acids was upregulated, thereby increasing the production of arachidonic acid in middle-stage J2 Meloidogyne incognita worms. We also found that arachidonic acid upregulated the expression of the transcription factor hlh-30b, which in turn induced lysosomal biogenesis. Lysosomes promoted lipid hydrolysis via a lysosomal lipase, LIPL-1. Furthermore, our data demonstrated that blockage of lysosomal lipolysis reduced both lifespan and locomotion of J2 worms. Strikingly, disturbance of lysosomal lipolysis resulted in a decline in infectivity of these juveniles on tomato roots. Our findings not only reveal the molecular mechanism of lipolysis in J2 worms but also suggest potential novel strategies for the management of root-knot nematode pests.

Uncovering the anti-biofilm activity of Ilicicolin B against Staphylococcus aureus.

The formation of bacterial biofilms reduces the entry of antibiotics into bacteria and helps bacteria tolerate otherwise lethal concentrations of antimicrobials, leading to antibiotic resistance. Therefore, clearing bacterial biofilm is an effective strategy to tackle drug resistance. Currently, there are no approved antibiotics for inhibiting bacterial biofilm formation. We found that Ilicicolin B had excellent antibacterial activity against MRSA without obvious hemolytic activity. More importantly, Ilicicolin B effectively inhibited the biofilm formation in a concentration-dependent manner by crystal violet colorimetric assay and fluorescence microscopy analysis. Exposure of Staphylococcus aureus to Ilicicolin B for 24 h reduced the protein and polysaccharide components in EPS, suggesting that Ilicicolin B disintegrated the biofilms by dissociating the EPS in a matrix. In addition, Ilicicolin B demonstrated strong antibacterial effects in a murine abscess model of S. aureus. Our findings suggest that Ilicicolin B has the potential to treat S. aureus infection by inhibiting biofilm formation.

The EGL-30 pathway regulates experience-dependent aversive behavior of Caenorhabditis elegans to the pathogenic bacterium Pseudomonas aeruginosa.

Avoidance of harmful substances is survival strategy used cross invertebrates and vertebrates. For example, the nematode Caenorhabditis elegans evolves a sufficient avoidance response to pathogenic bacteria. Despite G protein has been found to exert neural plasticity for avoidance behaviours in C. elegans, the function of Gi/o and Gq subunit signalling in experience-dependent aversive behaviour remains unclear. In this study, we show that EGL-30/Gq coupled with EGL-8/UNC-13 regulates aversive behaviour of C. elegans to pathogenic bacterium Pseudomonas aeruginosa PA01 via acetylcholine and its receptor nAChR. Pyocyanin, a toxin secreted from P. aeruginosa, acts as a signal molecule to trigger aversive behaviour. ODR-3 and ODR-7 in AWA and AWC neurons function as upstream of EGL-30 to induce experience-dependent aversive behaviour to P. aeruginosa, respectively. These results suggested that a novel signalling pathway to regulate a behavioural response.

Endoscopic cyanoacrylate injection therapy for refractory high-risk peptic ulcer bleeding by conventional endoscopic therapy.

OBJECTIVE: To evaluate the efficacy and safety of endoscopic cyanoacrylate injection therapy for refractory high-risk peptic ulcer bleeding by conventional endoscopic therapy. METHODS: 154 patients with refractory high-risk peptic ulcer bleeding by conventional endoscopic therapy at the Affiliated Hospital of Zunyi Medical Univesity and the People's Hospital of Liupanshui City from January 2018 to December 2021were enrolled in this study. Endoscopic intracellular cyanoacrylate injection was first carried out. When failure, perintravascullar injection was carried out. The data were retrospectively collected. RESULTS: Among the 154 patients, 102 patients (66.23%) obtained successful intravascular injection and perivascular injection was performed in 52 patients (33.77%). Immediate hemostatic rate for active bleeding achieved 93.18%. Overall rebleeding rate within 30 days was 12.99% and successful hemostasis rate achieved 87.01%. Immediate hemostatic rate and successful hemostasis rate in intravascular injection patients were markedly superior over perivascular injection. Rebleeding rate in intravascular injection patients was markedly lower than that in perivascular injection patients. 14 patients complicated abdominal pain and no other complication occurred. CONCLUSION: Endoscopic cyanoacrylate injection therapy, especial intravascular injection, was effective and safe, with high successful hemostasis rate for refractory high-risk peptic ulcer bleeding by conventional endoscopic therapy.

Balanced electro-optical properties and off-axis haze performance of a polymer-dispersed liquid crystal film via refractive index matching.

As a type of smart dimming film, polymer-dispersed liquid crystals (PDLCs) show great prospects in the fields of indoor partition, electronic curtains, and automobile windows. However, its high off-axis haze greatly impacts the application scope. This obvious shortcoming is mainly caused by the serious mismatch between the effective refractive index of the liquid crystal (neff) and the refractive index of the polymer matrix (np) at large viewing angles. Thereby, factors affecting the viewing angle of a PDLC film are analyzed in this research, including the birefringence of the liquid crystal (Δn), film thickness, and the refractive index of the polymer matrix (np). Balanced electro-optical properties are guaranteed simultaneously. It is found that high on-state transmittance and low off-axis haze can be achieved at large viewing angles in the suggested optimized case where Δn is within the range of 0.1-0.13; the film thickness is between 20 µm and 15 µm; and np approaches no but the difference does not exceed 0.03.

Improving efficiency and reducing enzyme inactivation during lipase-mediated epoxidation of α-pinene in a double-phase reaction system.

Chemoenzymatic epoxidation of olefin mediated by lipase is a green and environmentally friendly alternative process. However, the mass transfer barrier and lipase deactivation caused by the traditional organic-water biphasic reaction system have always been the focus of researchers' attention. To overcome these issues, we investigated the effects of reaction temperature and two important substrates (H2O2 and acyl donor) on the epoxidation reaction and interfacial mass transfer. As a result, we determined the optimal reaction conditions: a temperature of 30 °C, 30 wt-% H2O2 as the oxygen source, and 1 M lauric acid as the oxygen carrier. Additionally, by simulating the conditions of shaking flask reactions, we designed a batch reactor and added a metal mesh to effectively block the direct contact between high-concentration hydrogen peroxide and the enzyme. Under these optimal conditions, the epoxidation reaction was carried out for 5 h, and the product yield reached a maximum of 93.2%. Furthermore, after seven repetitive experiments, the lipase still maintained a relative activity of 51.2%.

Application of Nicotinamide to Culture Medium Improves the Efficiency of Genome Editing in Hexaploid Wheat.

Histone acetylation is the earliest and most well-characterized of post-translation modifications. It is mediated by histone acetyltransferases (HAT) and histone deacetylases (HDAC). Histone acetylation could change the chromatin structure and status and further regulate gene transcription. In this study, nicotinamide, a histone deacetylase inhibitor (HDACi), was used to enhance the efficiency of gene editing in wheat. Transgenic immature and mature wheat embryos harboring a non-mutated GUS gene, the Cas9 and a GUS-targeting sgRNA were treated with nicotinamide in two concentrations (2.5 and 5 mM) for 2, 7, and 14 days in comparison with a no-treatment control. The nicotinamide treatment resulted in GUS mutations in up to 36% of regenerated plants, whereas no mutants were obtained from the non-treated embryos. The highest efficiency was achieved when treated with 2.5 mM nicotinamide for 14 days. To further validate the impact of nicotinamide treatment on the effectiveness of genome editing, the endogenous TaWaxy gene, which is responsible for amylose synthesis, was tested. Utilizing the aforementioned nicotinamide concentration to treat embryos containing the molecular components for editing the TaWaxy gene, the editing efficiency could be increased to 30.3% and 13.3%, respectively, for immature and mature embryos in comparison to the 0% efficiency observed in the control group. In addition, nicotinamide treatment during transformation progress could also improve the efficiency of genome editing approximately threefold in a base editing experiment. Nicotinamide, as a novel approach, may be employed to improve the editing efficacy of low-efficiency genome editing tools such as base editing and prime editing (PE) systems in wheat.

Mesoporous WS2-Decorated Cellulose Nanofiber-Templated CuO Heterostructures for High-Performance Chemiresistive Hydrogen Sulfide Sensors.

There is a great demand to develop high-performance hydrogen sulfide (H2S) sensors, especially at the trace level for environmental protection, human healthcare, and food freshness monitoring. To this end, cellulose nanofiber (CNF)-templated CuO (CuO-C) was decorated with tungsten disulfide (WS2) nanosheets (W-Cu-C) as the sensing layer of chemiresistive microelectromechanical system (MEMS) sensors for H2S recognition in this work. As compared to pristine CuO counterparts at 160.5 °C, the as-prepared W-Cu-C-10 sensors delivered a 30-fold enhanced response of 37 toward 0.5 ppm H2S at a lower optimal operation temperature of 100.1 °C. Moreover, a fast response/recovery speed of 37.2/33.9 s toward 0.5 ppm H2S and excellent long-term stability and selectivity were achieved. Compared with existing research and commercial products, the W-CU-C-10 sensors exhibited the remarkable superiorities of high sensitivity, the lowest detection limit of 200 ppb, and ultralow power consumption (8 mW). Also, the sensor showcased a nice on-site application potential for evaluating eggs' freshness. The proposed W-Cu-C-10 sensors probably pave a new avenue for designing high-sensitivity and energy-efficient future H2S sensors, especially in the fields of portable and wearable detection systems as well as Internet of Things.

YAP in epithelium senses gut barrier loss to deploy defenses against pathogens.

Pathogens commonly disrupt the intestinal epithelial barrier; however, how the epithelial immune system senses the loss of intestinal barrier as a danger signal to activate self-defense is unclear. Through an unbiased approach in the model nematode Caenorhabditis elegans, we found that the EGL-44/TEAD transcription factor and its transcriptional activator YAP-1/YAP (Yes-associated protein) were activated when the intestinal barrier was disrupted by infections with the pathogenic bacterium Pseudomonas aeruginosa PA14. Gene Ontology enrichment analysis of the genes containing the TEAD-binding sites revealed that "innate immune response" and "defense response to Gram-negative bacterium" were two top significantly overrepresented terms. Genetic inactivation of yap-1 and egl-44 significantly reduced the survival rate and promoted bacterial accumulation in worms after bacterial infections. Furthermore, we found that disturbance of the E-cadherin-based adherens junction triggered the nuclear translocation and activation of YAP-1/YAP in the gut of worms. Although YAP is a major downstream effector of the Hippo signaling, our study revealed that the activation of YAP-1/YAP was independent of the Hippo pathway during disruption of intestinal barrier. After screening 10 serine/threonine phosphatases, we identified that PP2A phosphatase was involved in the activation of YAP-1/YAP after intestinal barrier loss induced by bacterial infections. Additionally, our study demonstrated that the function of YAP was evolutionarily conserved in mice. Our study highlights how the intestinal epithelium recognizes the loss of the epithelial barrier as a danger signal to deploy defenses against pathogens, uncovering an immune surveillance program in the intestinal epithelium.

RBM38 in cancer: role and mechanism.

Cancer is the second leading cause of death globally. Abnormity in gene expression regulation characterizes the trajectory of tumor development and progression. RNA-binding proteins (RBPs) are widely dysregulated, and thus implicated, in numerous human cancers. RBPs mainly regulate gene expression post-transcriptionally, but emerging studies suggest that many RBPs can impact transcription by acting on chromatin as transcription factors (TFs) or cofactors. Here, we review the evidence that RBM38, an intensively studied RBP, frequently plays a tumor-suppressive role in multiple human cancer types. Genetic studies in mice deficient in RBM38 on different p53 status also establish RBM38 as a tumor suppressor (TS). By uncovering a spectrum of transcripts bound by RBM38, we discuss the diversity in its mechanisms of action in distinct biological contexts. Examination of the genomic features and expression pattern of RBM38 in human tissues reveals that it is generally lost but rarely mutated, in cancers. By assessing future trends in the study of RBM38 in cancer, we signify the possibility of targeting RBM38 and its related pathways as therapeutic strategies against cancer.

Cypermethrin inhibits Leydig cell development and function in pubertal rats.

Cypermethrin is a broad-spectrum pyrethroid insecticide that is widely used. It may induce adverse endocrine-disrupting effects on the male reproductive system. Whether cypermethrin can disrupt Leydig cell development and function in the late puberty remains elusive. The objective of this study was to explore the effect of cypermethrin exposure to male rats on the development and function of Leydig cells in late puberty and explore the underlying mechanism. Thirty-six male Sprague-Dawley rats (age of 35 days) were gavaged with cypermethrin (0, 12.5, 25, and 50 mg/kg/day) from postnatal day 35-49. Cypermethrin significantly lowered serum testosterone level while elevating serum luteinizing hormone level at a dose of 50 mg/kg, without altering serum follicle-stimulating hormone level. Cypermethrin markedly decreased CYP11A1-positive Leydig cell number at 50 mg/kg without affecting SOX9-positive Sertoli cell number. It significantly down-regulated the expression of Leydig cell genes, Lhcgr, Star, Cyp11a1, and Cyp17a1 and their proteins, while up-regulating the expression of Sertoli cell genes, Dhh and Amh, and their proteins, at doses of 12.5-50 mg/kg. In addition, cypermethrin significantly increased malondialdehyde level while lowering the expression of Sod1 and Sod2 and their proteins at 50 mg/kg. Cypermethrin markedly induced reactive oxidative species at a concentration of 200 µM and reduced mitochondrial membrane potential at 25 µM and higher concentrations after 24 h of treatment to primary Leydig cells in vitro. In conclusion, cypermethrin inhibits the development and function of Leydig cells in male rats in late puberty.