Rare variations within the serine/arginine-rich splicing factor PtoRSZ21 modulate stomatal size to determine drought tolerance in Populus.

Rare variants contribute significantly to the 'missing heritability' of quantitative traits. The genome-wide characteristics of rare variants and their roles in environmental adaptation of woody plants remain unexplored. Utilizing genome-wide rare variant association study (RVAS), expression quantitative trait loci (eQTL) mapping, genetic transformation, and molecular experiments, we explored the impact of rare variants on stomatal morphology and drought adaptation in Populus. Through comparative analysis of five world-wide Populus species, we observed the influence of mutational bias and adaptive selection on the distribution of rare variants. RVAS identified 75 candidate genes correlated with stomatal size (SS)/stomatal density (SD), and a rare haplotype in the promoter of serine/arginine-rich splicing factor PtoRSZ21 emerged as the foremost association signal governing SS. As a positive regulator of drought tolerance, PtoRSZ21 can recruit the core splicing factor PtoU1-70K to regulate alternative splicing (AS) of PtoATG2b (autophagy-related 2). The rare haplotype PtoRSZ21hap2 weakens binding affinity to PtoMYB61, consequently affecting PtoRSZ21 expression and SS, ultimately resulting in differential distribution of Populus accessions in arid and humid climates. This study enhances the understanding of regulatory mechanisms that underlie AS induced by rare variants and might provide targets for drought-tolerant varieties breeding in Populus.

Thermally Activated Delayed Fluorescence with Nanosecond Emission Lifetimes and Minor Concentration Quenching: Achieving High-Performance Nondoped and Doped Blue OLEDs.

Simultaneously achieving a high photoluminescence quantum yield (PLQY), ultrashort exciton lifetime, and suppressed concentration quenching in thermally activated delayed fluorescence (TADF) materials is desirable yet challenging. Here, a novel acceptor-donor-acceptor type TADF emitter, namely, 2BO-sQA, wherein two oxygen-bridged triarylboron (BO) acceptors are arranged with cofacial alignment and positioned nearly orthogonal to the rigid dispirofluorene-quinolinoacridine (sQA) donor is reported. This molecular design enables the compound to achieve highly efficient (PLQYs up to 99%) and short-lived (nanosecond-scale) blue TADF with effectively suppressed concentration quenching in films. Consequently, the doped organic light-emitting diodes (OLEDs) base on 2BO-sQA achieve exceptional electroluminescence performance across a broad range of doping concentrations, maintaining maximum external quantum efficiencies (EQEs) at over 30% for doping concentrations ranging from 10 to 70 wt%. Remarkably, the nondoped blue OLED achieves a record-high maximum EQE of 26.6% with a small efficiency roll-off of 14.0% at 1000 candelas per square meter. By using 2BO-sQA as the sensitizer for the multiresonance TADF emitter ν-DABNA, TADF-sensitized fluorescence OLEDs achieve high-efficiency deep-blue emission. These results demonstrate the feasibility of this molecular design in developing TADF emitters with high efficiency, ultrashort exciton lifetime, and minimal concentration quenching.

Retraction notice to: The optimality principle decreases hemodynamic stresses for aneurysm initiation at anterior cerebral artery bifurcations [WNEU 121 (2019) e379-e388/10317].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. It includes data and figures from patients that were cared for by Dr. Malek at the Cerebrovascular Hemodynamics laboratory in the Department of Neurosurgery at Tufts Medical Center. The Editor-in-Chief has been informed by Tufts Medical Center that the authors of the paper did not have clinical privileges for these patients and played no clinical role in their care.

Retraction notice to: Enlarged anterior cerebral artery bifurcation angles may induce abnormally enhanced hemodynamic stresses to initiate aneurysms [WNEU 120 (2018) e783-e791/9025].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. It includes data and figures from patients that were cared for by Dr. Malek at the Cerebrovascular Hemodynamics laboratory in the Department of Neurosurgery at Tufts Medical Center. The Editor-in-Chief has been informed by Tufts Medical Center that the authors of the paper did not have clinical privileges for these patients and played no clinical role in their care.

Transcriptome Dynamics during Spike Differentiation of Wheat Reveal Amazing Changes in Cell Wall Metabolic Regulators.

Coordinated cell proliferation and differentiation result in the complex structure of the inflorescence in wheat. It exhibits unique differentiation patterns and structural changes at different stages, which have attracted the attention of botanists studying the dynamic regulation of its genes. Our research aims to understand the molecular mechanisms underlying the regulation of spike development genes at different growth stages. We conducted RNA-Seq and qRT-PCR evaluations on spikes at three stages. Our findings revealed that genes associated with the cell wall and carbohydrate metabolism showed high expression levels between any two stages throughout the entire process, suggesting their regulatory role in early spike development. Furthermore, through transgenic experiments, we elucidated the role of the cell wall regulator gene in spike development regulation. These research results contribute to identifying essential genes associated with the morphology and development of wheat spike tissue.

Ecological risk assessment and restoration area identification of Pengyang County on the basis of the landscape pattern and function.

The joint landscape ecological risk as well as ecological corridors for ecological restoration area identification is of great significance to the past evolution and future development of landscapes. Ecological risks were assessed based on the landscape pattern and functional changes in Pengyang County in 2000, 2010, and 2020; ecological restoration areas were divided based on ecological risks and security pattern. Results showed that the ecological risk types in Pengyang County were mainly low risk from 2000 to 2010 and distributed in the central region, while the high-risk areas increased from 2010 to 2020 and were concentrated in the southern residential area. According to a comprehensive assessment of the landscape ecological risks, an ecological security pattern consisting of 17 ecological source points and 34 potential ecological corridors with an average length of 6.57 km was identified. Three ecological restoration areas were eventually identified: mining restoration areas, mountain restoration area, and urban restoration area. Our results would provide an important perspective for the sustainable development of regional natural landscape resources.

Functionalized human umbilical cord mesenchymal stem cells and injectable HA/Gel hydrogel synergy in endometrial repair and fertility recovery.

Intrauterine adhesions (IUA) caused by endometrial injury are one of the main causes of female infertility. The current treatments for endometrial injury offer limited clinical benefits and cannot improve endometrial receptivity and pregnancy outcomes. Tissue engineering and regenerative medicine are considered potential solutions to address this concern and may offer effective treatment methods for the regeneration of injured human endometrium. Herein, we prepared an injectable hydrogel based on oxidized hyaluronic acid (HA-CHO) and hydrazide-grafted gelatin (Gel-ADH). The injectable hydrogel showed satisfactory biocompatibility when mixed with human umbilical cord mesenchymal stem cells (hUCMSCs). In an endometrial injury rat model, the treatment with hUCMSCs-loaded injectable hydrogel significantly enhanced the thickness of the endometrium and increased the abundance of blood vessels and glands in the injured endometrium compared to the control group. The hUCMSCs-loaded injectable hydrogel treatment significantly reduced endometrial fibrosis, decreased the expression of the pro-inflammatory factors (IL-1ß and IL-6) and increased the expression of the anti-inflammatory factor (IL-10). This treatment induced endometrial VEGF expression by activating the MEK/ERK1/2 signaling pathway. Moreover, this treatment improved endometrial receptivity to the embryo and restored the embryo implantation rate similar to the sham group (48% in the sham group vs 46% in the treatment group), and this treatment achieved pregnancy and live birth in rats with endometrial injury. In addition, we also preliminarily validated the safety of this treatment in the maternal rats and fetuses. Collectively, our study showed that the hUCMSCs-loaded injectable hydrogel hold potential as an effective treatment strategy promoting rapid recovery of endometrial injury, and this hydrogel is a promising biomaterial for regenerative medicine applications. STATEMENT OF SIGNIFICANCE: 1. Oxidized hyaluronic acid (HA-CHO)/hydrazide-grafted gelatin (Gel-ADH) hydrogel combined with human umbilical cord mesenchymal stem cells (hUCMSCs) are effective in improving the regeneration of endometrium in the endometrial injury rat model. 2. The hUCMSCs-loaded hydrogel treatment promotes the expression of endometrial VEGF through MEK/ERK1/2 signaling pathway and regulates the balance of inflammatory factors. 3. The embryo implantation and live birth rates restore to normal level in the endometrial injury rat model, and the hydrogel has no adverse effects on maternal rats, fetuses, and offspring development after the treatments.

Reduced NCK1 participates in unexplained recurrent miscarriage by regulating trophoblast functions and macrophage proliferation at maternal-fetal interface.

Recurrent miscarriage (RM) seriously affects the physical and mental health of women of childbearing age, and 50% of the causes are unknown. Thus, it is valuable to investigate the causes of unexplained recurrent miscarriage (uRM). Similarities between tumor development and embryo implantation make us realize that tumor studies are informative for uRM. The non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1) is highly expressed in some tumors, and can promote tumor growth, invasion and migration. In this present paper, we firstly explore the role of NCK1 in uRM. We find that the NCK1 and PD-L1 are greatly reduced in peripheral blood mononuclear cells (PBMC) and decidua from patients with uRM. Next, we construct NCK1-knockdown HTR-8/SVneo cells, and find that NCK1-knockdown HTR-8/SVneo cells exhibit reduced proliferation and migration ability. Then we demonstrate that the expression of PD-L1 protein is decreased when the NCK1 is knocked down. In co-culture experiments with THP-1 and differently treated HTR-8/SVneo cells, we observe significantly increased proliferation of THP-1 in NCK1-knockdown group. In conclusion, NCK1 may be involved in RM by regulating trophoblast proliferation, migration, and regulating PD-L1-mediated macrophage proliferation at the maternal-fetal interface. Moreover, NCK1 has the potential to be a new predictor and therapeutic target.

Recovery of pinch force sense after short-term fatigue.

The aim of this study was to identify the exact origin of force sense and identify whether it arises centrally or peripherally. The present study was designed to analyze the effects of short-term fatigue on pinch force sense and the duration of these effects. During the fatigue protocol, twenty (10 men and 10 women; Mage = 22.0 years old) young Chinese participants were asked to squeeze maximally until the pinch grip force decreased to 50% of its maximal due to fatigue. Participants were instructed to produce the target force (10% of maximal voluntary isometric contraction) using the same hand before and after fatigue (immediately, 10, 30, 60, 180, 300 s). The results showed significantly higher absolute error immediately after fatigue (1.22 ± 1.06 N) than before fatigue (0.68 ± 0.34 N), and 60 s (0.76 ± 0.69 N), 180 s (0.67 ± 0.42 N), and 300 s (0.75 ± 0.37 N) after fatigue (all P < 0.05) but with no effect on the variable error (P > 0.05). It was also revealed that there was a significant overestimate of the constant error values before (0.32 ± 0.61 N) and immediately after fatigue (0.80 ± 1.38 N, all P < 0.05), while no significant overestimation or underestimation exceeded 300 s after fatigue (P > 0.05). Our study results revealed that short-term fatigue resulted in a significant decrease in force sense accuracy, but it did not affect force sense consistently; however, force sense accuracy recovered to a certain extent within 10 s and 30 s, whereas it recovered fully within 60 s, and force sense directivity improvement exceeded 300 s after fatigue. The present study shows that the sense of tension (peripherally) is also an important factor affecting force sense. Our study supports the view that the periphery is part of the origin of force sense.

Rational Design of Highly Efficient Orange-Red/Red Thermally Activated Delayed Fluorescence Emitters with Submicrosecond Emission Lifetimes.

The development of orange-red/red thermally activated delayed fluorescence (TADF) materials with both high emission efficiencies and short lifetimes is highly desirable for electroluminescence (EL) applications, but remains a formidable challenge owing to the strict molecular design principles. Herein, two new orange-red/red TADF emitters, namely AC-PCNCF3 and TAC-PCNCF3, composed of pyridine-3,5-dicarbonitrile-derived electron-acceptor (PCNCF3) and acridine electron-donors (AC/TAC) are developed. These emitters in doped films exhibit excellent photophysical properties, including high photoluminescence quantum yields of up to 0.91, tiny singlet-triplet energy gaps of 0.01 eV, and ultrashort TADF lifetimes of less than 1 µs. The TADF-organic light-emitting diodes employing the AC-PCNCF3 as emitter achieve orange-red and red EL with high external quantum efficiencies of up to 25.0% and nearly 20% at doping concentrations of 5 and 40 wt%, respectively, both accompanied by well-suppressed efficiency roll-offs. This work provides an efficient molecular design strategy for developing high-performance red TADF materials.

Efficient Spin-Flip between Charge-Transfer States for High-Performance Electroluminescence, without an Intermediate Locally Excited State.

Thermally activated delayed fluorescence (TADF) materials with both high photoluminescence quantum yield (PLQY) and fast reverse intersystem crossing (RISC) are strongly desired to realize efficient and stable organic light-emitting diodes (OLEDs). Control of excited-state dynamics via molecular design plays a central role in optimizing the PLQY and RISC rate of TADF materials but remains challenging. Here, 3 TADF emitters possessing similar molecular structures, similar high PLQYs (89.5% to 96.3%), and approximate energy levels of the lowest excited singlet states (S1), but significantly different spin-flipping RISC rates (0.03 × 106 s-1 vs. 2.26 × 106 s-1) and exciton lifetime (297.1 to 332.8 µs vs. 6.0 µs) were systematically synthesized to deeply investigate the feasibility of spin-flip between charge-transfer excited states (3CT-1CT) transition. Experimental and theoretical studies reveal that the small singlet-triplet energy gap together with low RISC reorganization energy between the 3CT and 1CT states could provide an efficient RISC through fast spin-flip 3CT-1CT transition, without the participation of an intermediate locally excited state, which has previously been recognized as being necessary for realizing fast RISC. Finally, the OLED based on the champion TADF emitter achieves a maximum external quantum efficiency of 27.1%, a tiny efficiency roll-off of 4.1% at 1,000 cd/m2, and a high luminance of 28,150 cd/m2, which are markedly superior to those of the OLEDs employing the other 2 TADF emitters.

Decreased B7-H3 promotes unexplained recurrent miscarriage via RhoA/ROCK2 signaling pathway and regulates the secretion of decidual NK cells†.

The cause for at least 50% of recurrent miscarriages is unclear, which is defined as unexplained recurrent miscarriages. The B7-H1 (PD-L1), a molecule of the B7 family, promotes tumor development by modulating immune evasion, and recent researchers have also attached importance to the role of B7-H3, another molecule of B7 family, in tumor. Based on the similarity between growth and immune response in tumors and pregnancy, we first explored the role of B7-H3 in unexplained recurrent miscarriages. We found reduced levels of B7-H3 in the villus tissue of unexplained recurrent miscarriage patients, and it was mainly expressed on the cell membrane of extravillous trophoblasts. Further, the HTR-8/SVneo and JEG-3 cells were selected to explore the role of B7-H3 in proliferation, apoptosis, tube formation, migration, and invasion. We found that B7-H3 regulated trophoblast migration and invasion via RhoA/ROCK2 signaling pathway. Inflammatory cytokines were detected through enzyme-linked immunosorbent assay after co-culturing with decidual natural killer cells and B7-H3-knockout JEG-3. Results showed that B7-H3 inhibited IL-8 and IP-10 secretion from the decidual natural killer cells. In a CBA/J × DBA/2 abortion-prone mice model, treatment with B7-H3-Fc protein successfully reduced the rate of embryo resorption. In conclusion, our results revealed a possible mechanism by which decreased B7-H3 on trophoblasts of unexplained recurrent miscarriages inhibited trophoblast migration and invasion and increased IL-8 and IP-10 secretion from the decidual natural killer cells. Furthermore, B7-H3 may be a promising new therapeutic target in unexplained recurrent miscarriage patients.

The effect of pinch span on pinch force sense in healthy participants.

The purpose of the current investigation was to evaluate the effect of pinch span on the perception of pinch force in typical participants. The healthy participants (10 males and 10 females) conducted an ipsilateral force reproduction test with three distinct pinch spans (2, 4, and 6 cm) at three distinct forces of 10%, 30%, and 50% maximum voluntary isometric contraction. The findings revealed a significantly greater consistency (lower variable error (VE)) of 4 cm compared with 2 and 6 cm pinch spans. Our study also showed that the participants might use a larger force (more overestimated) output for larger pinch spans (4 and 6 cm) than small pinch spans (2 cm). These results may offer significant insights into the higher rates of musculoskeletal disorders among females, enabling researchers and clinicians to design novel interventions and tools to improve pinch force perception and reduce hand injury rates in males and females.

VitroGel-loaded human MenSCs promote endometrial regeneration and fertility restoration.

Introduction: Intrauterine adhesions (IUA), also known as Asherman's syndrome, is caused by trauma to the pregnant or non-pregnant uterus, which leads to damaged endometrial basal lining and partial or total occlusion of the uterine chambers, resulting in abnormal menstruation, infertility, or recurrent miscarriage. The essence of this syndrome is endometrial fibrosis. And there is no effective treatment for IUA to stimulate endometrial regeneration currently. Recently, menstrual blood-derived stem cells (MenSCs) have been proved to hold therapeutic promise in various diseases, such as myocardial infarction, stroke, diabetes, and liver cirrhosis. Methods: In this study, we examined the effects of MenSCs on the repair of uterine adhesions in a rat model, and more importantly, promoted such therapeutic effects via a xeno-free VitroGel MMP carrier. Results: This combined treatment reduced the expression of inflammatory factors, increased the expression of anti-inflammatory factors, restricted the area of endometrial fibrosis, diminished uterine adhesions, and partially restored fertility, showing stronger effectiveness than each component alone and almost resembling the sham group. Discussion: Our findings suggest a highly promising strategy for IUA treatment.

The role of macrophages in reproductive-related diseases.

The study of reproductive immunology includes the role of immunity in reproductive physiology and reproductive-related diseases. Reproductive-related diseases cause low pregnancy rate mainly through ovulation disorders, low-quality sperm production, embryo implantation failure and pregnancy maintenance disorders. Numerous cell types including infiltrating immune cells perform specific functions in the reproductive system. Physiologically macrophages are enriched in the decidua and testes, and macrophages are involved in endometrial receptivity, embryo implantation and spermatogenesis. Pathologically macrophages are associated with alterations of decidual microenvironment in recurrent implantation failure (RIF) and unexplained recurrent miscarriage (uRM), local inflammation in polycystic ovary syndrome (PCOS) and clearance of endometriotic lesions in endometriosis. Although researchers have recently attempted to uncover the pathogenesis and provide effective treatments for the reproductive-related diseases, the specific mechanisms and effective therapies need to be further explored. Here we summarized the latest mechanisms by which macrophages participate in the progression of the reproductive-related diseases, and the promising immune-based treatments. In addition, we discussed decidual macrophage classification and the importance of immune networks in reproduction-related diseases.

Carboniferous slab-retreating subduction of backarc oceans: the final large-scale lateral accretion of the southern Central Asian Orogenic Belt.

During Carboniferous time, tremendous juvenile arc crust was formed in the southern Central Asian Orogenic Belt (CAOB), although its origin remains unclear. Herein, we presented zircon U-Pb-Hf and whole-rock geochemical and Sr-Nd isotopic data for a suite of volcanic and pyroclastic rocks from the Khan-Bogd area in southern Mongolia. These Carboniferous pyroclastic rocks generally have some early Paleozoic zircons, probably derived from the granitic and sedimentary rocks of the Lake Zone and the Gobi-Altai Zone to the north, indicative of a continental arc nature. In addition, they have a main zircon U-Pb age of ca. 370-330 Ma, positive Hf and Nd isotopes, and mafic-intermediate arc affinity, similar to the coeval arc magmatism. Moreover, the pyroclastic rocks of the northern area have more mafic and older volcanic components with depositional time (ca. 350-370 Ma; Visean and Bashkirian stages) earlier than that in the southern area (mainly ca. 350-315 Ma; Serpukhovian and Bashkirian stages). Combining a preexisting northward subduction supported by the available magnetotelluric data with a slab rollback model of the main oceanic basin of the Paleo-Asian Ocean (PAO) during Carboniferous and Triassic times, we infer that the Carboniferous arc magmatism was probably derived from a backarc ocean triggered by slab rollback. Thus, the juvenile arc volcanism of Mongolia, together with other areas (e.g., Junggar) in the southern CAOB, represented a significant lateral accretion that terminated after the Carboniferous due to a significant contraction of the PAO.

PD-L1 enhances migration and invasion of trophoblasts by upregulating ARHGDIB via transcription factor PU.1.

As the main constituent cells of the human placenta, trophoblasts proliferate, differentiate, and invade the uterine endometrium via a series of processes, which are regulated exquisitely through intercellular signaling mediated by hormones, cytokines, and growth factors. Programmed cell death ligand 1 (PD-L1) is a biomarker of the response to immune checkpoint inhibitors and can regulate maternal-fetal immune tolerance during pregnancy progression. Recently, it was found that PD-L1 may regulate obstetric complications by affecting the function of trophoblasts. Therefore, we examined the expression and localization of PD-L1 in the human placenta and observed the effects of PD-L1 on trophoblasts migration and invasion in both the trophoblasts line HTR-8/SVneo and an extravillous explant culture model. Finally, we explored the molecular mechanisms underlying PD-L1-regulated trophoblasts migration and invasion through RNA sequencing and bioinformatics analysis. Our data showed that PD-L1 was mainly expressed in syncytiotrophoblasts and that its protein levels increased with gestational age. Interestingly, the protein expression of PD-L1 was significantly decreased in placentas from pregnancies with preeclampsia compared with normal placentas. Importantly, the migration and invasion abilities of trophoblasts were significantly changed after knockdown or overexpression of PD-L1 in HTR-8/SVneo cells and an extravillous explant culture model, which was partially mediated through the transcription factor PU.1 (encoded by Spi1)-regulated Rho GDP-dissociation inhibitor beta (ARHGDIB) expression. These results suggested that PD-L1 was highly involved in the regulation of trophoblasts migration and invasion, providing a potential target for the diagnosis and treatment of placenta-derived pregnancy disorders.

Ultrahigh Energy Storage Density and High Efficiency in Lead-Free (Bi0.9Na0.1)(Fe0.8Ti0.2)O3-Modified NaNbO3 Ceramics via Stabilizing the Antiferroelectric Phase and Enhancing Relaxor Behavior.

Dielectric capacitors have attracted growing attention because of their important applications in advanced high power and/or pulsed power electronic devices. Nevertheless, the synergistic enhancement of recoverable energy storage density (Wrec > 10 J/cm3) and efficiency (η > 80%) is still a great challenge for lead-free dielectric bulk ceramics. Herein, by introducing complex perovskite compound (Bi0.9Na0.1)(Fe0.8Ti0.2)O3 with a smaller tolerance factor into an NaNbO3 matrix (NN-BNFT), we have achieved and explored stable relaxor antiferroelectric ceramics with enhanced relaxor behavior. Of particular importance is the composition of 0.88NN-0.12BNFT, which exhibits a large electric breakdown strength Eb of 87.3 kV/mm, an ultrahigh Wrec of 12.7 J/cm3, and a high efficiency η of 82.5%, as well as excellent thermal reliability and an ultrafast discharge speed, resulting from the dense microstructure, the moderate dielectric constant, the reduced grain size, the dielectric loss, and the sample thickness. The outstanding energy storage properties of NN-BNFT display great promise in advanced dielectric capacitors for energy storage applications.