Glycyrrhizin attenuates myocardial ischemia reperfusion injury by suppressing Inflammation, oxidative stress, and ferroptosis via the HMGB1-TLR4-GPX4 pathway.

Ferroptosis, a form of regulated cell death process, play an important role in myocardial ischemia‒reperfusion (I/R) injury. Glycyrrhizin (GL), a natural glycoconjugate triterpene, has the property to improve growth rate, immune regulation, antioxidant, anti-inflammatory. However, whether GL can attenuate myocardial I/R injury by modulating ferroptosis or other mechanisms are still unclear. In this study, SD rats underwent in vivo myocardial ischemia/reperfusion (I/R) surgery, while H9C2 cells were subjected to the hypoxia/reoxygenation (H/R) model for in vitro experiments. In addition, TAK-242, a TLR4-specific antagonist, and GL were also used to evaluate the effect and mechanisms of GL on the cardiac function and expression of ferroptosis-related gene and protein in vivo and vitro. The results show that GL decreased not only the expression of the inflammation-related factors (HMGB1, TNF-α, IL-6, IL-18 and IL-1ß), but also reduced the number of TUNEL-positive cardiomyocytes, and mitigated pathological alterations in I/R injury. In addition, GL decreased the levels of MDA, promoted antioxidant capacity such as GSH, CAT, Cu/Zn-SOD, Mn-SOD, and SOD in vivo and vitro. More importantly, GL and TAK-242 regulate ferroptosis-related protein and gene expression in I/R and H/R model. Surprisingly, GL may ameliorate cardiomyocyte ferroptosis and ultimately improves cardiac function induced by H/R via the HMGB1-TLR4-GPX4 axis. Therefore, we have highlighted a novel mechanism by which GL regulates inflammation, oxidative stress, and ferroptosis via the HMGB1-TLR4-GPX4 pathway to prevent myocardial I/R injury. GL appears to be a potentially applicable drug for the treatment of myocardial I/R injury.

Orbital Interactions in 2D Dion-Jacobson Perovskites Using Oligothiophene-Based Semiconductor Spacers Enable Efficient Solar Cells.

2D Dion-Jacobson (DJ) perovskites have emerged as promising photovoltaic materials, but the insulating organic spacer has hindered the efficient charge transport. Herein, we successfully synthesized a terthiophene-based semiconductor spacer, namely, 3ThDMA, for 2D DJ perovskite. An interesting finding is that the energy levels of 3ThDMA extensively overlap with the inorganic components and directly contribute to the band formation of (3ThDMA)PbI4, leading to enhanced charge transport across the organic spacer layers, whereas no such orbital interactions were found in (UDA)PbI4, a DJ perovskite based on 1,11-undecanediaminum (UDA). The devices based on (3ThDMA)MAn-1PbnI3n+1 (nominal n = 5) obtained a champion efficiency of 15.25%, which is a record efficiency for 2D DJ perovskite solar cells using long-conjugated spacers (conjugated rings ≥ 3) and a 22.60% efficiency for 3ThDMA-treated 3D PSCs. Our findings provide an important insight into understanding the orbital interactions in 2D DJ perovskite using an organic semiconductor spacer for efficient solar cells.

Single-Crystal-Assisted In Situ Phase Reconstruction Enables Efficient and Stable 2D/3D Perovskite Solar Cells.

Perovskite solar cells (PSCs) that incorporate both two-dimensional (2D) and three-dimensional (3D) phases possess the potential to combine the high stability of 2D PSCs with the superior efficiency of 3D PSCs. Here, we demonstrated in situ phase reconstruction of 2D/3D perovskites using a 2D perovskite single-crystal-assisted method. A gradient phase distribution of 2D RP perovskites was formed after spin-coating a solution of the 2D Ruddlesden-Popper (RP) perovskite single crystal, (DFP)2PbI4, onto the 3D perovskite surface, followed by thermal annealing. The resulting film exhibits much reduced trap density, increased carrier mobility, and superior water resistance. As a result, the optimized 2D/3D PSCs achieved a champion efficiency of 24.87% with a high open-circuit voltage (VOC) of 1.185 V. This performance surpasses the control 3D perovskite device, which achieved an efficiency of 22.43% and a VOC of 1.129 V. Importantly, the unencapsulated device demonstrates significantly enhanced operational stability, preserving over 97% of its original efficiency after continuous light irradiation for 1500 h. Moreover, the extrapolated T80 lifetimes surpass 5700 h. These findings pave the way for rational regulation of the gradient phase distribution at the interface between 2D and 3D perovskites by employing 2D RP perovskite crystals to achieve stable and efficient PSCs.

Multiarmed Aromatic Ammonium Salts Boost the Efficiency and Stability of Inverted Organic Solar Cells.

Inverted organic solar cells (OSCs) have attracted much attention because of their outstanding stability, with zinc oxide (ZnO) being commonly used as the electron transport layer (ETL). However, both surface defects and the photocatalytic effect of ZnO could lead to serious photodegradation of acceptor materials. This, in turn, hampers the improvement of the efficiency and stability in OSCs. Herein, we developed a multiarmed aromatic ammonium salt, namely, benzene-1,3,5-triyltrimethanaminium bromide (PhTMABr), for modifying ZnO. This compound possesses mild weak acidity aimed at removing the residual amines present within ZnO film. In addition, the PhTMABr could also passivate surface defects of ZnO through multiple hydrogen-bonding interactions between its terminal amino groups and the oxygen anion of ZnO, leading to a better interface contact, which effectively enhances charge transport. As a result, an efficiency of 18.75% was achieved based on the modified ETL compared to the bare ZnO (PCE = 17.34%). The devices utilizing the modified ZnO retained 87% and 90% of their initial PCE after thermal stress aging at 65 °C for 1500 h and continuous 1-sun illumination with maximum power point (MPP) tracking for 1780 h, respectively. Importantly, the extrapolated T80 lifetime with MPP tracking exceeds 10 000 h. The new class of materials employed in this work to modify the ZnO ETL should pave the way for enhancing the efficiency and stability of OSCs, potentially advancing their commercialization process.

Crystal Growth Regulation of Ruddlesden-Popper Perovskites via Self-Assembly of Semiconductor Spacers for Efficient Solar Cells.

The crystal growth and orientation of two-dimensional (2D) perovskite films significantly impact solar cell performance. Here, we incorporated robust quadrupole-quadrupole interactions to govern the crystal growth of 2D Ruddlesden-Popper (RP) perovskites. This was achieved through the development of two unique semiconductor spacers, namely PTMA and 5FPTMA, with different dipole moments. The ((5FPTMA)0.1 (PTMA)0.9 )2 MAn-1 Pbn I3n+1 (nominal n=5, 5F/PTMA-Pb) film shows a preferred vertical orientation, reduced grain boundaries, and released residual strain compared to (PTMA)2 MAn-1 Pbn I3n+1 (nominal n=5, PTMA-Pb), resulting in a decreased exciton binding energy and reduced electron-phonon coupling coefficients. In contrast to PTMA-Pb device with an efficiency of 15.66 %, the 5F/PTMA-Pb device achieved a champion efficiency of 18.56 %, making it among the best efficiency for 2D RP perovskite solar cells employing an MA-based semiconductor spacer. This work offers significant insights into comprehending the crystal growth process of 2D RP perovskite films through the utilization of quadrupole-quadrupole interactions between semiconductor spacers.

Progress in molecular mechanisms of coronary microvascular dysfunction.

Coronary microvascular dysfunction is a high-risk factor for many cardiovascular events. However, because of multiple risk factors and limited understanding about its underlying pathophysiological mechanisms, it was easily misdiagnosed. Therefore, its clinical diagnosis and treatment were greatly restricted. Coronary microcirculation refers to microvessels that play an important role in the physiological regulation of myocardial perfusion and regulating blood flow distribution, fulfilling myocardial metabolic needs and moderating peripheral vascular resistance. In coronary microvascular dysfunction, vascular endothelial celldamage is a critical link. The main feature of early coronary microvascular dysfunction is the impairment of endothelial cell proliferation, adhesion, migration, apoptosis, and secretion. Moreover, coronary microvascular dysfunction risk factors include hyperglycemia, lipid metabolism disorders, ischemia-reperfusion injury, aging, and hypertension, similar to coronary atherosclerosis. There are various mechanisms by which these risk factors harm endothelial function and cause microcirculatory disturbances. Therefore, we reviewed coronary microvascular dysfunction's risk factors and pathogenesis in this article.

Dimensional Tuning of Perylene Diimide-Based Polymers for Perovskite Solar Cells with Over 24% Efficiency.

The hygroscopic dopants used in Spiro-OMeTAD hole transport material (HTM) in state-of-the-art perovskite solar cells (PSCs) inevitably induce premature degradation of the devices. Here, two multifunctional polymer interface materials based on the perylene diimides (PDI) unit are developed. It is found that quasi-two-dimensional (2D) polymer 2DP-PDI can form a denser film and exhibit better hydrophobicity than linear polymer P-PDI. Importantly, 2DP-PDI can passivate the surface defects and extract hole carriers of perovskite film more effectively, leading to much reduced nonradiative recombination loss. With polymer interface material between the perovskite and HTM layers, the optimized device using 2DP-PDI and P-PDI yields a champion PCE of 24.20% and 23.09%, respectively, along with significantly improved stability, whereas the control device shows a lower efficiency of 22.23%. These results suggest that developing multifunctional polymer interface materials can be a promising strategy to improve the efficiency and stability of PSCs.

Chiral Naphthalenediimides with High-Efficiency Fluorescence and Circularly Polarized Luminescence in the Solid State for the Application in Organic Optoelectronics.

Naphthalenediimides (NDIs) have been extensively studied due to their tunable luminescent properties. However, generally, the monomers or aggregates of non-core substituted NDIs exhibit low fluorescence quantum yields (ΦFL <10 %) in the solid state, which limit their applications as light-emitting materials and render their chiral species unsuitable for circularly polarized luminescence (CPL). Herein, a series of non-core substituted chiral NDIs that exhibit high luminous efficiencies (ΦFL up to 56.8 % for racemate and 36.5 % for enantiomer) and a strong CPL behavior in the solid state is reported. These significant improvements are attributed to the unique molecular conformation of the chiral NDIs and the formation of distinctive discrete dimers. The structures of the NDIs were significantly simpler and more accessible than those of other NDIs. The findings evidence that non-core substituted NDIs can exhibit strong fluorescence in the solid state and provide a new pathway to improve photophysical properties of NDIs.

Nucleation and Crystallization in 2D Ruddlesden-Popper Perovskites using Formamidinium-based Organic Semiconductor Spacers for Efficient Solar Cells.

The conjugated organic semiconductor spacers have drawn wide attention in two-dimensional (2D) perovskites and formamidinium (FA) has been widely used as A-site cation in high-performance 3D perovskite solar cells (PSCs). However, the FA-based semiconductor spacers have rarely been investigated in 2D Ruddlesden-Popper (RP) perovskites. Here, we developed two FA-based spacers containing thieno[3,2-b]thiophene (TT) and 2,2'-bithiophene (BT) units, namely TTFA and BTFA, respectively, for 2D RP PSCs. The nucleation and crystallization kinetics of TTFA-Pb and BTFA-Pb from sol-gel to film were investigated using in situ optical microscopy and in situ grazing incidence wide-angle X-ray scattering (GIWAXS) measurements. It is found that the TTFA spacer could reduce the energy barrier of nucleation and induces crystal vertical orientation of 2D perovskite by forming larger clusters in precursor solution, resulting in much improved film quality. Benefiting from the enlarged crystal grains, reduced exciton binding energy, and decreased electron-phonon coupling coefficient, the photovoltaic device based on (TTFA)2 MAn-1 Pbn I3n+1 (n=5) achieved a champion efficiency of 19.41 %, which is a record for 2D RP PSCs with FA-based spacers. Our work provides deep understanding of the nucleation and crystallization process of 2D RP perovskite films and highlights the great potential of FA-based semiconductor spacers in highly efficient 2D PSCs.

[Clinical and genetic analysis of a Chinese pedigree affected with Dyggve-Melchior-Clausen syndrome due to a novel frameshift variant of DYM gene].

OBJECTIVE: To explore the genetic basis of a Chinese pedigree affected with Dyggve-Melchior-Clausen syndrome. METHODS: Whole exome sequencing and Sanger sequencing were carried out to detect potential pathogenic variants associated with the syndrome. The function of candidate variant was verified by Western blotting. RESULTS: A novel homozygous variant, c.1222delG of the DYM gene was detected in the two affected siblings, for which both parents were heterozygous carriers. The variant has caused replacement of Asp by Met at amino acid 408 and generate a premature stop codon p.Asp408Metfs*10. Western blotting confirmed that the variant can result in degradation of the mutant DYM protein, suggesting that it is a loss of function variant. CONCLUSION: The homozygous c.1222delG frameshift variant of the DYM probably underlay the Dyggve-Melchior-Clausen syndrome in the two affected siblings. Above findings has enabled clinical diagnosis and genetic counseling for the family.

PET neuroimaging reveals upregulation of dopamine D2 receptor contributes to amygdaloid dysfunction in rat acute restraint stress model.

Acute stress relates to high prevalence of anxiety, depression or even sudden death. Although dopaminergic system in amygdala-medial prefrontal cortex (mPFC) circuit is hyper-responsive to stress-induced anxiety, the mechanisms that control anxiety still remains unanswered. Here, the acute restraint stress model(ARS) was established to develop anxiety-like behavior. The D2-dopamine receptor (D2R) availability in amygdala and mPFC was assessed using [18F]-fallypride positron emission tomography(PET) and immunohistochemical assay. We revealed that ARS paradigm was successfully established, as evidenced by elevated plus-maze test(EPM) and increased corticosterone release. Moreover, PET imaging displayed elevated D2R availability in the amygdala and mPFC in ARS as compared to that in the naives. PET imaging combined with immunohistochemical assay confirmed that amygdaloid D2R was significantly implicated in stress-induced anxiety. Our findings delivered valuable insights into neuromechanism of amygdaloid D2R underlying stress-induced anxiety and might have important implications for developing therapeutics for anxiety by targeting amygdaloid D2R.

Loss of SPACA1 function causes autosomal recessive globozoospermia by damaging the acrosome-acroplaxome complex.

STUDY QUESTION: Is the sperm acrosome membrane-associated protein 1 (SPACA1) gene critical to human globozoospermia? SUMMARY ANSWER: The biallelic loss-of-function (variant of SPACA1) causes globozoospermia as a result of acrosome-acroplaxome complex damage. WHAT IS KNOWN ALREADY: SPACA1 expression decreases in patients with globozoospermia. Spaca1 gene-disrupted mice have abnormally shaped sperm heads that resemble those of human globozoospermia. STUDY DESIGN, SIZE, DURATION: We recruited a consanguineous family with two brothers affected by infertility as a consequence of globozoospermia. The semen analysis data and ART outcomes were collected. Exome sequencing (ES) was used to identify potential pathogenic variants. Protein-protein interaction (PPI) technologies and proteomic analysis were utilized to explore the pathogenic mechanism. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two globozoospermic brothers and their consanguineous parents were recruited to identify the potential pathogenic variant through ES. A homozygous nonsense variant in the SPACA1 gene in both brothers inherited from the heterozygous parents was identified. Twenty normal fertile males were recruited as controls. Sperm ultrastructure was observed with transmission electron microscopy. Western blotting was performed to measure SPACA1 expression level in the sperm from the patients. Mass spectrometry (MS) analyses were used to identify differentially expressed proteins and to investigate proteins that interact with SPACA1. Co-immunoprecipitation (co-IP), yeast two-hybrid (Y2H) and immunofluorescence colocalization assays were used to confirm the PPI. MAIN RESULTS AND THE ROLE OF CHANCE: A nonsense variant (NM_030960.2: c.53G>A; p. Trp18*) in the SPACA1 gene was identified as the pathogenic variant in a family with globozoospermia. Patient IV:1 and Patient IV:2 had a phenotype very similar to that of Spaca1 gene-disrupted mice. The nonsense variant in SPACA1 led to premature transcriptional termination in the signal peptide, which was confirmed by western blotting. MS-based proteomics analysis showed that eight interactors of SPACA1 were differentially expressed in the patients' sperm, including actin-like Protein 7A (ACTL7A), an important component of the acrosome-acroplaxome complex. The PPI of SPACA1 and ACTL7A was confirmed via co-IP and Y2H assays. Immunofluorescence showed that SPACA1 and ACTL7A colocalized in mature sperm, revealing that these proteins were coexpressed spatially. LIMITATIONS, REASONS FOR CAUTION: Given the rarity of globozoospermia, only two patients from one family harbouring the SPACA1 variant were found. Future studies should evaluate SPACA1 variants in larger cohorts to corroborate this finding. WIDER IMPLICATIONS OF THE FINDINGS: This study revealed that the SPACA1 gene was critical for globozoospermia, which expanded the spectrum of causative genes for globozoospermia. This study also provided evidence for ICSI clinical outcomes for patients with SPACA1-deficient globozoospermia, which may guide clinical treatment strategies. Furthermore, this study explored the pathogenesis of globozoospermia caused by SPACA1 deficiency. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Precision Medical Research of National Key Research and Development Program (2018YFC1002400), National Natural Science Foundation of China (81873724), and Natural Science Foundation of Shanghai (20ZR1472700). The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Numerical investigation on turbulent oscillatory flow through a jet pump.

A jet pump with an asymmetrical channel can induce a time-averaged pressure drop in oscillatory flow, which can effectively suppress Gedeon streaming in looped thermoacoustic engines. In this work, the flow characteristics and time-averaged pressure drop caused by a jet pump in turbulent oscillatory flow are investigated through numerical simulation. Through the analysis of the dimensionless governing equations, the emphasis is put on the effects of Womersley number and maximum acoustic Reynolds number on the performance of the jet pump. Meanwhile, the steady flow resistance coefficients are also measured numerically. The results indicate that the oscillatory flow resistance coefficients are relatively insensitive to Womersley number when it is less than 46. Moreover, the oscillatory flow resistance coefficients agree well with the steady state flow results, which validate the quasi-static assumption in turbulent oscillatory flow. However, further increasing Womersley number will lead to a reduction in the time-averaged pressure drop. The simulation method and results, as well as the hydrodynamic mechanism beneath the results, are presented and discussed in detail.

ATF4 regulates CCL2 expression to promote endometrial cancer growth by controlling macrophage infiltration.

Activating transcription factor 4 (ATF4), an endoplasmic reticulum stress-inducible transcription factor, plays important roles in cancer progression and resistance to therapy. However, no report is available about its roles in endometrial cancer (EC). In this study, we found that ATF4 is commonly expressed in EC cell lines. Loss-of-function studies in two EC cell lines showed that ATF4 knockdown suppresses tumor growth of EC in vivo without influencing cell proliferation in vitro. And xenograft tumors derived from ATF4-knockdown cells had reduced M2 macrophage infiltration. In clinical specimens, ATF4-high expressing tumors indeed contained more macrophage infiltration compared to those with lower ATF4 expression. Moreover, we identified that ATF4-mediated chemokine CCL2 expression ultimately results in macrophage infiltration and tumor growth of EC. Taken together, our findings suggest that ATF4 contributes to tumor growth of EC by promoting CCL2 and subsequent recruitment of macrophage, and that ATF4/CCL2 axis might be a potential therapeutic target for EC.

Improving the Performance of Multi-GNSS Time and Frequency Transfer Using Robust Helmert Variance Component Estimation.

The combination of multiple Global Navigation Satellite Systems (GNSSs) may improve the performance of time and frequency transfers by increasing the number of available satellites and improving the time dilution of precision. However, the receiver clock estimation is easily affected by the inappropriate weight of multi-GNSSs due to the different characteristics of individual GNSS signals as well as the outliers from observations. Thus, we utilised a robust Helmert variance component estimation (RVCE) approach to determine the appropriate weights of different GNSS observations, and to control for the influence of outliers in these observation in multi-GNSS time and frequency transfer. In order to validate the effectiveness of this approach, four time links were employed. Compared to traditional solutions, the mean improvement of smoothed residuals is 3.43% using the RVCE approach. With respect to the frequency stability of the time links, the RVCE solution outperforms the traditional solution, particularly in the short-term, and the mean improvement is markedly high at 14.89%.

Enhancement of open-circuit voltage and the fill factor in CdTe nanocrystal solar cells by using interface materials.

Interface states influence the operation of nanocrystal (NC) solar cell carrier transport, recombination and energetic mechanisms. In a typical CdTe NC solar cell with a normal structure of a ITO/p-CdTe NCs/n-acceptor (or without)/Al configuration, the contact between the ITO and CdTe is a non-ohm contact due to a different work function (for an ITO, the value is ~4.7 eV, while for CdTe NCs, the value is ~5.3 eV), which results in an energetic barrier at the ITO/CdTe interface and decreases the performance of the NC solar cells. This work investigates how interface materials (including Au, MoO(x) and C60) affect the performance of NC solar cells. It is found that devices with interface materials have shown higher V(oc) than those without interface materials. For the case in which we used Au as an interface, we obtained a high open-circuit voltage of 0.65 V, coupled with a high fill factor (62%); this resulted in a higher energy conversion efficiency (ECE) of 5.3%, which showed a 30% increase in the ECE compared with those without the interlayer. The capacitance measurements indicate that the increased V(oc) in the case in which Au was used as the interface is likely due to good ohm contact between the Au's and the CdTe NCs' thin film, which decreases the energetic barrier at the ITO/CdTe interface.

Controlled Nucleation and Oriented Crystallization of Methylammonium-Free Perovskites via In Situ Generated 2D Perovskite Phases.

Enhancing stability while maintaining high efficiency is among the primary challenges in the commercialization of perovskite solar cells (PSCs). Here, a crystal growth technique assisted by in situ generated 2D perovskite phases has been developed to construct high-quality 2D/3D perovskite films. The in situ generated 2D perovskite serve as templates for regulating the nucleation and oriented crystal growth in the α-FAPbI3-rich film. This led to a high film quality with much reduced trap density and an ultralong carrier lifetime. The obtained perovskite film shows excellent stability under extreme environment conditions (T = 200 °C, RH = 75 ± 5%). The corresponding PSC achieved an efficiency of 26.16% (certified 25.84%), along with excellent operational stability (T93 > 1300 h, T ≅ 50 °C) as well as outstanding high and low temperature cycle stability.

Recent Progress of Layered Perovskite Solar Cells Incorporating Aromatic Spacers.

Layered two dimensional (2D) or quasi-2D perovskites are emerging photovoltaic materials due to their superior environment and structure stability in comparison with their 3D counterparts. The typical 2D perovskites can be obtained by cutting 3D perovskites along < 100 > orientation by incorporation of bulky organic spacers, which play a key role in the performance of 2D perovskite solar cells (PSCs). Compared with aliphatic spacers, aromatic spacers with high dielectric constant have the potential to decrease the dielectric and quantum confinement effect of 2D perovskites, promote efficient charge transport and reduce the exciton binding energy, all of which are beneficial for the photovoltaic performance of 2D PSCs. In this review, we aim to provide useful guidelines for the design of aromatic spacers for 2D perovskites. We systematically reviewed the recent progress of aromatic spacers used in 2D PSCs. Finally, we propose the possible design strategies for aromatic spacers that may lead to more efficient and stable 2D PSCs.

Perspectives and Considerations of IABP in the Era of ECMO for Cardiogenic Shock.

The development of mechanical circulatory support (MCS) has been rapid, and its use worldwide in patients with cardiogenic shock is increasingly widespread. However, current statistical data and clinical research do not demonstrate its significant improvement in the patient prognosis. This review focuses on the widely used intra-aortic balloon pumps (IABP) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO), analyzing and comparing their characteristics, efficacy, risk of complications, and the current exploration status of left ventricular mechanical unloading. Subsequently, we propose a rational approach to viewing the negative outcomes of current MCS, and look ahead to the future development trends of IABP.