Deploying a Dipole Electric Field at the CsPbI3 Perovskite/Carbon Interface for Enhancing Hole Extraction and Photovoltaic Performance.

Carbon-based CsPbI3 perovskite solar cells without hole transporter (C-PSCs) have achieved intense attention due to its simple device structure and high chemical stability. However, the severe interface energy loss at the CsPbI3/carbon interface, attributed to the lower hole selectivity for inefficient charge separation, greatly limits device performance. Hence, dipole electric field (DEF) is deployed at the above interface to address the above issue by using a pole molecule, 4-trifluoromethyl-Phenylammonium iodide (CF3-PAI), in which the ─NH3 group anchors on the perovskite surface and the ─CF3 group extends away from it and connects with carbon electrode. The DEF is proven to align with the built-in electric field, that is pointing toward carbon electrode, which well enhances hole selectivity and charge separation at the interface. Besides, CF3-PAI molecules also serve as defect passivator for reducing trap state density, which further suppresses defect-induced non-radiative recombination. Consequently, the CsPbI3 C-PSCs achieve an excellent efficiency of 18.33% with a high VOC of 1.144 V for inorganic C-PSCs without hole transporter.

Electronic structure modulation of iron sites with fluorine coordination enables ultra-effective H2O2 activation.

Electronic structure modulation of active sites is critical important in Fenton catalysis as it offers a promising strategy for boosting H2O2 activation. However, efficient generation of hydroxyl radicals (•OH) is often limited to the unoptimized coordination environment of active sites. Herein, we report the rational design and synthesis of iron oxyfluoride (FeOF), whose iron sites strongly coordinate with the most electronegative fluorine atoms in a characteristic moiety of F-(Fe(III)O3)-F, for effective H2O2 activation with potent •OH generation. Results demonstrate that the fluorine coordination plays a pivotal role in lowering the local electron density and optimizing the electronic structures of iron sites, thus facilitating the rate-limiting H2O2 adsorption and subsequent peroxyl bond cleavage reactions. Consequently, FeOF exhibits a significant and pH-adaptive •OH yield (~450 µM) with high selectivity, which is 1 ~ 3 orders of magnitude higher than the state-of-the-art iron-based catalysts, leading to excellent degradation activities against various organic pollutants at neutral condition. This work provides fundamental insights into the function of fluorine coordination in boosting Fenton catalysis at atomic level, which may inspire the design of efficient active sites for sustainable environmental remediation.

Spatially selective defect management of CsPbI3 films for high-performance carbon-based inorganic perovskite solar cells.

Defects formed at the surface, buried interface and grain boundaries (GB) of CsPbI3 perovskite films considerably limit photovoltaic performance. Such defects could be passivated effectively by the most prevalent post modification strategy without compromising the photoelectric properties of perovskite films, but it is still a great challenge to make this strategy comprehensive to different defects spatially distributed throughout the films. Herein, a spatially selective defect management (SSDM) strategy is developed to roundly passivate various defects at different locations within the perovskite film by a facile one-step treatment procedure using a piperazine-1,4-diium tetrafluoroborate (PZD(BF4)2) solution. The small-size PZD2+ cations could penetrate into the film interior and even make it all the way to the buried interface of CsPbI3 perovskite films, while the BF4- anions, with largely different properties from I- anions, mainly anchor on the film surface. Consequently, virtually all the defects at the surface, buried interface and grain boundaries of CsPbI3 perovskite films are effectively healed, leading to significantly improved film quality, enhanced phase stability, optimized energy level alignment and promoted carrier transport. With these films, the fabricated CsPbI3 PSCs based on carbon electrode (C-PSCs) achieve an efficiency of 18.27%, which is among the highest-reported values for inorganic C-PSCs, and stability of 500 h at 85 °C with 65% efficiency maintenance.

Remote Ischemic Conditioning Mediates Cardio-protection After Myocardial Ischemia/Reperfusion Injury by Reducing 4-HNE Levels and Regulating Autophagy via the ALDH2/SIRT3/HIF1α Signaling Pathway.

Remote ischemic conditioning (RIC) can be effectively applied for cardio-protection. Here, to clarify whether RIC exerts myocardial protection via aldehyde dehydrogenase 2 (ALDH2), we established a myocardial ischemia/reperfusion (I/R) model in C57BL/6 and ALDH2 knockout (ALDH2-KO) mice and treated them with RIC. Echocardiography and single-cell contraction experiments showed that RIC significantly improved myocardial function and alleviated I/R injury in C57BL/6 mice but did not exhibit its cardioprotective effects in ALDH2-KO mice. TUNEL, Evan's blue/triphenyl tetrazolium chloride, and reactive oxygen species (ROS) assays showed that RIC's effect on reducing myocardial cell apoptosis, myocardial infarction area, and ROS levels was insignificant in ALDH2-KO mice. Our results showed that RIC could increase ALDH2 protein levels, activate sirtuin 3 (SIRT3)/hypoxia-inducible factor 1-alpha (HIF1α), inhibit autophagy, and exert myocardial protection. This study revealed that RIC could exert myocardial protection via the ALDH2/SIRT3/HIF1α signaling pathway by reducing 4-HNE secretion.

SASH1: A Novel Eph Receptor Partner and Insights into SAM-SAM Interactions.

The Eph (erythropoietin-producing human hepatocellular) receptor family, the largest subclass of receptor tyrosine kinases (RTKs), plays essential roles in embryonic development and neurogenesis. The intracellular Sterile Alpha Motif (SAM) domain presents a critical structural feature that distinguishes Eph receptors from other RTKs and participates in recruiting and binding downstream molecules. This study identified SASH1 (SAM and SH3 domain containing 1) as a novel Eph receptor-binding partner through SAM-SAM domain interactions. Our comprehensive biochemical analyses revealed that SASH1 selectively interacts with Eph receptors via its SAM1 domain, displaying the highest affinity for EphA8. The high-resolution crystal structure of the EphA8-SASH1 complex provided insights into the specific intermolecular interactions between these proteins. Cellular assays confirmed that EphA8 and SASH1 co-localize and co-precipitate in mammalian cells, with cancer mutations (EphA8 R942H or G978D) impairing this interaction. We demonstrated that SAM-SAM interaction is critical for SASH1-mediated regulation of EphA8 kinase activity, shedding new light on the Eph signaling pathway and expanding our understanding of the molecular basis of the tumor suppressor gene SASH1.

m6A demethylase ALKBH5 attenuates doxorubicin-induced cardiotoxicity via posttranscriptional stabilization of Rasal3.

The clinical application of anthracyclines such as doxorubicin (DOX) is limited due to their cardiotoxicity. N6-methyladenosine (m6A) plays an essential role in numerous biological processes. However, the roles of m6A and m6A demethylase ALKBH5 in DOX-induced cardiotoxicity (DIC) remain unclear. In this research, DIC models were constructed using Alkbh5-knockout (KO), Alkbh5-knockin (KI), and Alkbh5-myocardial-specific knockout (ALKBH5flox/flox, αMyHC-Cre) mice. Cardiac function and DOX-mediated signal transduction were investigated. As a result, both Alkbh5 whole-body KO and myocardial-specific KO mice had increased mortality, decreased cardiac function, and aggravated DIC injury with severe myocardial mitochondrial damage. Conversely, ALKBH5 overexpression alleviated DOX-mediated mitochondrial injury, increased survival, and improved myocardial function. Mechanistically, ALKBH5 regulated the expression of Rasal3 in an m6A-dependent manner through posttranscriptional mRNA regulation and reduced Rasal3 mRNA stability, thus activating RAS3, inhibiting apoptosis through the RAS/RAF/ERK signaling pathway, and alleviating DIC injury. These findings indicate the potential therapeutic effect of ALKBH5 on DIC.

ADAD2 interacts with RNF17 in P-bodies to repress the Ping-pong cycle in pachytene piRNA biogenesis.

Pachytene piRNA biogenesis is a hallmark of the germline, distinct from another wave of pre-pachytene piRNA biogenesis with regard to the lack of a secondary amplification process known as the Ping-pong cycle. However, the underlying molecular mechanism and the venue for the suppression of the Ping-pong cycle remain elusive. Here, we showed that a testis-specific protein, ADAD2, interacts with a TDRD family member protein RNF17 and is associated with P-bodies. Importantly, ADAD2 directs RNF17 to repress Ping-pong activity in pachytene piRNA biogenesis. The P-body localization of RNF17 requires the intrinsically disordered domain of ADAD2. Deletion of Adad2 or Rnf17 causes the mislocalization of each other and subsequent Ping-pong activity derepression, secondary piRNAs overproduced, and disruption of P-body integrity at the meiotic stage, thereby leading to spermatogenesis arrested at the round spermatid stage. Collectively, by identifying the ADAD2-dependent mechanism, our study reveals a novel function of P-bodies in suppressing Ping-pong activity in pachytene piRNA biogenesis.

Ultrasensitive Linear Capacitive Pressure Sensor with Wrinkled Microstructures for Tactile Perception.

Ultrasensitive flexible pressure sensors with excellent linearity are essential for achieving tactile perception. Although microstructured dielectrics have endowed capacitive sensors with ultrahigh sensitivity, the compromise of sensitivity with increasing pressure is an issue yet to be resolved. Herein, a spontaneously wrinkled MWCNT/PDMS dielectric layer is proposed to realize the excellent sensitivity and linearity of capacitive sensors for tactile perception. The synergistic effect of a high dielectric constant and wrinkled microstructures enables the sensor to exhibit linearity up to 21 kPa with a sensitivity of 1.448 kPa-1 and a detection limit of 0.2 Pa. Owing to these merits, the sensor monitors subtle physiological signals such as various arterial pulses and respiration. This sensor is further integrated into a fully multimaterial 3D-printed soft pneumatic finger to realize material hardness perception. Eight materials with different hardness values are successfully discriminated, and the capacitance of the sensor varies linearly (R2 > 0.975) with increasing hardness. Moreover, the sensitivity to the material hardness can be tuned by controlling the inflation pressure of the soft finger. As a proof of concept, the finger is used to discriminate pork fats with different hardness, paving the way for hardness discrimination in clinical palpation.

Comparative transcriptome analysis of grafting to improve chilling tolerance of cucumber.

Grafting with pumpkin as rootstock could improve chilling tolerance of cucumber; however, the underlying mechanism of grafting-induced chilling tolerance remains unclear. Here, we analyzed the difference of physiological and transcriptional level between own-rooted (Cs/Cs) and hetero-grafted (Cs/Cm) cucumber seedlings under chilling stress. The results showed that grafting with pumpkin significantly alleviated the chilling injury as evidenced by slightly symptoms, lower contents of electrolyte leakage (EL), malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion (O2-) and higher relative water content in Cs/Cm seedlings compared with Cs/Cs seedlings under chilling stress. RNA-seq data showed that grafting induced more DGEs at 8 °C/5 °C compared with 25 °C/18 °C. In accordance with the increase of the activities of antioxidant enzymes (SOD, POD, CAT, APX), grafting upregulated the expression of the regulated redox-related genes such as GST, SOD, and APX. Moreover, grafting increased the expression of genes participated in central carbon metabolism to promote the conversion and decomposition of sugar, which provided more energy for the growth of Cs/Cm seedlings under chilling stress. In addition, grafting regulated the genes involved in the intracellular signal transduction pathways such as calcium signal (CAML, CML, and CDPK) and inositol phospholipid signal (PLC), as well as changed the gene expression of plant hormone signal transduction pathways (ARF, GAI, ABF, and PYR/PYL). These results provide a physiological and transcriptional basis for the molecular mechanism of grafting-induced chilling tolerance of cucumber seedlings.

hnRNPH1 establishes Sertoli-germ cell crosstalk through cooperation with PTBP1 and AR, and is essential for male fertility in mice.

Spermatogenesis depends on the crosstalk of Sertoli cells (SCs) and germ cells. However, the gene regulatory network establishing the communications between SCs and germ cells remains unclear. Here, we report that heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) in SCs is essential for the establishment of crosstalk between SCs and germ cells. Conditional knockout of hnRNPH1 in mouse SCs leads to compromised blood-testis barrier function, delayed meiotic progression, increased germ cell apoptosis, sloughing of germ cells and, eventually, infertility of mice. Mechanistically, we discovered that hnRNPH1 could interact with the splicing regulator PTBP1 in SCs to regulate the pre-mRNA alternative splicing of the target genes functionally related to cell adhesion. Interestingly, we also found hnRNPH1 could cooperate with the androgen receptor, one of the SC-specific transcription factors, to modulate the transcription level of a group of genes associated with the cell-cell junction and EGFR pathway by directly binding to the gene promoters. Collectively, our findings reveal a crucial role for hnRNPH1 in SCs during spermatogenesis and uncover a potential molecular regulatory network involving hnRNPH1 in establishing Sertoli-germ cell crosstalk.

Construction of metal-organic framework/polymer beads for efficient lead ions removal from water: Experiment studies and full-scale performance prediction.

Metal-organic frameworks (MOFs) show great promise in heavy metal removal; however, their applications are restricted by the poor separability and water instability. Herein, granular Zr-based MOF-polymer composite beads (MPCB(Zr)) (mean diameter âˆ¼ 1.74 mm) were synthesized using a facile dropping method, and applied on efficient lead ions (Pb(II)) removal. The as-prepared MPCB(Zr) demonstrated deep Pb(II) removal capability by reducing its concentration to âˆ¼ 0.002 mg L-1 after adsorption equilibrium at 360 min. The distribution coefficient for Pb(II) reached 8.0 × 106 mL g-1, and the theoretical adsorption capacity for Pb(II) was 144.5 mg g-1 (0.70 mmol g-1, 30 °C). The resulting MPCB(Zr) was highly selective for Pb(II), with the selectivity coefficient up to âˆ¼ 1.0-3.6 × 103 for the background cations (Na(I), K(I), Ca(II), and Mg(II)). Moreover, the MPCB(Zr) exhibited a broad working pH range (3.0-6.0) and satisfactory anti-interference to dissolved organic matters (humic acid and fuvic acid). Notably, the MPCB(Zr) also demonstrated excellent reusability with the Pb(II) removal efficiency over 99.0% after 20 cycles. Combined physicochemical characterizations unveiled that the thiol and oxygen-containing groups (e.g., hydroxyl, carboxylate) were responsible for the effective Pb(II) removal. To provide guidance for engineering application, the full-scale performance of the MPCB(Zr) under varying operation conditions was systematically evaluated via the validated pore surface diffusion model. This work provides an effective methodology to construct macroscopic MOF-polymer beads for effective Pb(II) removal, and promote the actual application of MOFs in water treatment.

UHRF1 establishes crosstalk between somatic and germ cells in male reproduction.

Sertoli cells (SCs) support and nourish germ cells (GCs) through their crosstalk during spermatogenesis. However, the underlying epigenetic mechanism that ensures SCs' functions in this process remains unclear. Here, we report that UHRF1, a critical epigenetic regulator, is mainly expressed in human and mouse pre-mature SCs, and is essential for establishing Sertoli-Germ cell crosstalk. SC-specific UHRF1 knockout mice exhibit complete sterility with Sertoli cell (SC) proliferation and differentiation aberrance, blood-testis barrier (BTB) disruption, and immature germ cell (GC) sloughing. RNA sequencing and Whole Genome Bisulfite Sequencing (WGBS) revealed that many extracellular matrix (ECM)-related genes (e.g., Timp1, Trf, and Spp1) appeared upregulated with the DNA hypomethylation status in UHRF1-deficient SCs. Strikingly, overexpression of Timp1, Trf, and Spp1 in SCs in vitro and in vivo could phenocopy the SC-specific UHRF1-deficient mice. Our data demonstrated that UHRF1 regulates the transcriptional program of ECM-related genes in SCs and establishes SC-GC crosstalk.

H2O2 participates in ABA regulation of grafting-induced chilling tolerance in cucumber.

KEY MESSAGE: Rootstock provides more abscisic acid (ABA) content to scions to increase the chilling tolerance of seedlings. H2O2 is involved in ABA regulation of grafting-induced chilling tolerance of cucumber. Here we examined the role of ABA in the response of grafted cucumber to chilling stress. The data showed chilling induced an increase in leaf and root ABA content and there was a positive correlation between ABA content and the chilling tolerance of the varieties. The increase of ABA content and NCED mRNA abundance in the leaf of both Cs/Cs (self-root) and Cs/Cm (grafted with pumpkin as rootstock) showed a delay under aerial stress compared with those under whole plant and root-zone stress. Intriguingly, an increase in ABA in xylem was found under whole-plant and root-zone chilling stress but was not detected under aerial stress, implying the increases in ABA content in leaves were mainly from root ABA transportation. Compared to Cs/Cs, a higher ABA content and NCED mRNA abundance were observed in Cs/Cm, which showed that Cm could output more ABA than Cs. The removal of endogenous ABA decreased the difference in chilling tolerance induced by Cm, as evidenced by the observed similar oxidative stress levels and photosynthetic capacity between Cs/Cs and Cs/Cm after chilling stress. Moreover, we found that the H2O2 signal in grafted cucumber could respond to chilling stress earlier than the H2O2 signal in self-rooted cucumber. The inhibition of endogenous H2O2 decreased the chilling tolerance of grafted cucumber induced by ABA by reducing photosynthesis and the mRNA abundance of CBF1 and COR. Thus, our results indicate that H2O2, as the downstream signal, participated in the rootstock-induced chilling tolerance of grafted seedlings induced by ABA.

Superselective Hg(II) Removal from Water Using a Thiol-Laced MOF-Based Sponge Monolith: Performance and Mechanism.

Point-of-use (POU) devices with satisfying mercury (Hg) removal performance are urgently needed for public health and yet are scarcely reported. In this study, a thiol-laced metal-organic framework (MOF)-based sponge monolith (TLMSM) has been investigated for Hg(II) removal as the POU device for its benchmark application. The resulting TLMSM was characterized by remarkable chemical resistance, mechanical stability, and hydroscopicity (>2100 wt %). Importantly, the TLMSM has exhibited high adsorption capacity (∼954.7 mg g-1), fast kinetics (kf ∼ 1.76 × 10-5 ms-1), broad working pH range (1-10), high selectivity (Kd > 5.0 × 107 mL g-1), and excellent regeneration capability (removal efficiency >90% after 25 cycles). The high applicability of TLMSM in real-world scenarios was verified by its excellent Hg(II) removal performance in various real water matrices (e.g., surface waters and industrial effluents). Moreover, a fixed-bed column test demonstrated that ∼1485 bed volumes of the feeding streams (∼500 µg L-1) can be effectively treated with an enrichment factor of 12.6, suggesting the great potential of TLMSM as POU devices. Furthermore, the principal adsorption complexes (e.g., single-layer -S-Hg-Cl and double-layer -S-Hg-O-Hg-Cl and -S-Hg-O-Hg-OH) formed during the adsorption process under a wide range of pH were synergistically and systematically unveiled using advanced tools. Overall, this work presents an applicable approach by tailoring MOF into a sponge substrate to achieve its real application in heavy metal removal from water, especially for Hg(II).

WDFY1, a WD40 repeat protein, is not essential for spermatogenesis and male fertility in mice.

The mouse WD repeat and FYVE domain containing 1 (Wdfy1) gene is located in chromosome 1qC4 and spans over 73.7 kilobases. It encodes a protein of 410-amino acid protein that shares 97.8% amino acid sequence identity with the human WDFY1 protein. However, the expression pattern of WDFY1 in reproductive organs and its function in male fertility remain unknown. In this study, we generated transgenic mice expressing FLAG-Wdfy1-mCherry cDNA driven by the Wdfy1 promoter to clarify the expression of WDFY1. The results showed that WDFY1 is highly expressed in mouse testes and located in the cytoplasm of late pachytene spermatocytes to elongated spermatids. Interestingly, the global Wdfy1 knockout (KO) male mice displayed normal growth, development, and fertility. Further histological analysis of Wdfy1 knockout mouse testes revealed that all spermatogenic cells are present in Wdfy1 KO seminiferous tubules. Together, our data demonstrate that WDFY1 is dispensable for mouse spermatogenesis and male fertility.

hnRNPU in Sertoli cells cooperates with WT1 and is essential for testicular development by modulating transcriptional factors Sox8/9.

Background: Sertoli cells are essential regulators of testicular fate in the differentiating gonad; however, its role and underlying molecular mechanism of regulating testicular development in prepubertal testes are poorly understood. Although several critical regulatory factors of Sertoli cell development and function have been identified, identifying extrinsic factors that regulate gonocyte proliferation and migration processes during neonatal testis development remains largely unknown. Methods: We used the Sertoli cell-specific conditional knockout strategy (Cre/Loxp) in mice and molecular biological analyses (Luciferase assay, ChIP-qPCR, RNA-Seq, etc.) in vitro and in vivo to study the physiological roles of hnRNPU in Sertoli cells on regulating testicular development in prepubertal testes. Results: We identified a co-transcription factor, hnRNPU, which is highly expressed in mouse and human Sertoli cells and required for neonatal Sertoli cell and pre-pubertal testicular development. Conditional knockout of hnRNPU in murine Sertoli cells leads to severe testicular atrophy and male sterility, characterized by rapid depletion of both Sertoli cells and germ cells and failure of spermatogonia proliferation and migration during pre-pubertal testicular development. At molecular levels, we found that hnRNPU interacts with two Sertoli cell markers WT1 and SOX9, and enhances the expression of two transcriptional factors, Sox8 and Sox9, in Sertoli cells by directly binding to their promoter regions. Further RNA-Seq and bioinformatics analyses revealed the transcriptome-wide of key genes essential for Sertoli cell and germ cell fate control, such as biological adhesion, proliferation and migration, were deregulated in Sertoli cell-specific hnRNPU mutant testes. Conclusion: Our findings demonstrate an essential role of hnRNPU in Sertoli cells for prepubertal testicular development and testis microenvironment maintenance and define a new insight for our understanding of male infertility therapy.

LncRNA LINC00473 promoted colorectal cancer cell proliferation and invasion by targeting miR-195 expression.

Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in cancer development. However, the role of LINC00473 in colorectal cancer has not been explored. In our study, we showed that LINC00473 expression was upregulated in colorectal cancer samples compared to nontumor samples. The expression of LINC00473 in colorectal cancer tissues from patients with distant metastasis was higher than that from cases without distant metastasis. The higher expression level of LINC00473 was positively correlated with advanced clinical stage. The elevated expression of LINC00473 accelerated colorectal cancer cell proliferation, cell cycle progression and invasion. Moreover, overexpression of LINC00473 induced epithelial to mesenchymal (EMT) progression in HT29 and SW480 cells. Ectopic expression of LINC00473 suppressed miR-195 expression in colorectal cancer cells. miR-195 expression was downregulated in colorectal cancer samples compared with nontumor samples. The expression of miR-195 in colorectal cancer tissues from patients with distant metastasis was lower than that from cases without distant metastasis. The lower expression level of miR-195 was positively correlated with advanced clinical stage. In addition, we showed that the expression of miR-195 was negatively correlated with the LINC00473 expression level in colorectal cancer tissues. LINC00473 accelerated colorectal cancer cell proliferation and cell cycle progression and regulated EMT progression by regulating miR-195 expression. These data suggested that LINC00473 induced cell proliferation, cell cycle progression and EMT progression by acting as a ceRNA for miR-195 in colorectal cancer.

The covalent NLRP3-inflammasome inhibitor Oridonin relieves myocardial infarction induced myocardial fibrosis and cardiac remodeling in mice.

BACKGROUND: Myocardial infarction (MI) triggers a strong inflammatory response that is associated with myocardial fibrosis and cardiac remodeling. Interleukin (IL)-1ß and IL-18 are key players in this response and are controlled by NLRP3-inflammatory bodies. Oridonin is a newly reported NLRP3 inhibitor with strong anti-inflammatory activity. We hypothesized that the covalent NLRP3 inhibitor Oridonin could reduce IL-1ß and IL-18 expression and ameliorate myocardial fibrosis after myocardial infarction in mice, improve poor heart remodeling, and preserve heart function. METHODS: Male C57BL/6 mice were subjected to left coronary artery ligation to induce MI and then treated with Oridonin (1, 3, or 6 mg/kg), MCC950 (10 mg/kg), CY-09 (5 mg/kg) or saline three times a week for two weeks. Four weeks after MI, cardiac function and myocardial fibrosis were assessed. In addition, myocardial expressions of inflammatory factors and fibrotic markers were analyzed by western blot, immunofluorescence, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. RESULTS: Oridonin treatment preserved left ventricular ejection fraction and fractional shortening, and markedly limited the myocardial infarct size in treated mice. The myocardial fibrosis was lower in the 1 mg/kg group (15.98 ± 1.64)%, 3 mg/kg group (17.39 ± 2.45)%, and 6 mg/kg group (16.76 ± 3.06)% compared to the control group (23.38 ± 1.65)%. Moreover, similar with the results of Oridonin, MCC950 and CY-09 also preserved cardiac function and reduced myocardial fibrosis. The expression levels of NLRP3, IL-1ß and IL-18 were decreased in the Oridonin treatment group compared to non-treated group. In addition, myocardial macrophage and neutrophil influxes were attenuated in the Oridonin treated group. CONCLUSIONS: The covalent NLRP3-inflammasome inhibitor Oridonin reduces myocardial fibrosis and preserves cardiac function in a mouse MI model, which indicates potential therapeutic effect of Oridonin on acute MI patients.

Role of Selective Autophagy in Spermatogenesis and Male Fertility.

Autophagy is a "self-eating" process that engulfs cellular contents for their subsequent digestion in lysosomes to engage the metabolic need in response to starvation or environmental insults. According to the contents of degradation, autophagy can be divided into bulk autophagy (non-selective autophagy) and selective autophagy. Bulk autophagy degrades non-specific cytoplasmic materials in response to nutrient starvation while selective autophagy targets specific cargoes, such as damaged organelles, protein aggregates, and intracellular pathogens. Selective autophagy has been documented to relate to the reproductive processes, especially for the spermatogenesis, fertilization, and biosynthesis of testosterone. Although selective autophagy is vital in the field of reproduction, its role and the underlying mechanism have remained unclear. In this review, we focus on selective autophagy to discuss the recent advances in our understanding of the mechanism and role of selective autophagy on spermatogenesis and male fertility in mammals. Understanding the role of selective autophagy during spermatogenesis will promote the recognition of genetic regulation in male infertility, and shed light on therapies of infertile patients.

Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond.

Multiple specific granular structures are present in the cytoplasm of germ cells, termed nuage, which are electron-dense, non-membranous, close to mitochondria and/or nuclei, variant size yielding to different compartments harboring different components, including intermitochondrial cement (IMC), piP-body, and chromatoid body (CB). Since mitochondria exhibit different morphology and topographical arrangements to accommodate specific needs during spermatogenesis, the distribution of mitochondria-associated nuage is also dynamic. The most relevant nuage structure with mitochondria is IMC, also called pi-body, present in prospermatogonia, spermatogonia, and spermatocytes. IMC is primarily enriched with various Piwi-interacting RNA (piRNA) proteins and mainly functions as piRNA biogenesis, transposon silencing, mRNA translation, and mitochondria fusion. Importantly, our previous work reported that mitochondria-associated ER membranes (MAMs) are abundant in spermatogenic cells and contain many crucial proteins associated with the piRNA pathway. Provocatively, IMC functionally communicates with other nuage structures, such as piP-body, to perform its complex functions in spermatogenesis. Although little is known about the formation of both IMC and MAMs, its distinctive characters have attracted considerable attention. Here, we review the insights gained from studying the structural components of mitochondria-associated germinal structures, including IMC, CB, and MAMs, which are pivotal structures to ensure genome integrity and male fertility. We discuss the roles of the structural components in spermatogenesis and piRNA biogenesis, which provide new insights into mitochondria-associated germinal structures in germ cell development and male reproduction.