Natural Amino Acid-Bearing Carbamate Prodrugs of Daidzein Increase Water Solubility and Improve Phase II Metabolic Stability for Enhanced Oral Bioavailability.

Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4'-O-CO-N-isoleucine, D-4'-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma. In addition, unlike the passive transport of DAN, D-4'-I maintained high permeability via organic anion-transporting polypeptide 2B1 (OATP2B1)-mediated transport. Importantly, D-4'-I increased the oral bioavailability by 15.5-fold, reduced the gender difference, and extended the linear absorption capacity in the pharmacokinetics of DAN in rats. Furthermore, D-4'-I exhibited dose-dependent protection against liver injury. Thus, the natural amino acid-bearing carbamate prodrug strategy shows potential in increasing water solubility and improving phase II metabolic stability to enhance the oral bioavailability of DAN.

Emerging non-antibody‒drug conjugates (non-ADCs) therapeutics of toxins for cancer treatment.

The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins. In recent years, toxins have been widely used as warheads for antibody‒drug conjugates (ADCs) due to their efficient killing activity against various cancer cells. Although ADCs confer certain targeting properties to the toxins, low drug loading capacity, possible immunogenicity, and other drawbacks also limit the potential application of ADCs. Recently, non-ADC delivery strategies for toxins have been extensively investigated. To further understand the application of toxins in anti-tumor, this paper provided an overview of prodrugs, nanodrug delivery systems, and biomimetic drug delivery systems. In addition, toxins and their combination strategies with other therapies were discussed. Finally, the prospect and challenge of toxins in cancer treatment were also summarized.

Thermal performance and experimental analysis of stainless steel flat plate solar collector with full-flow channels.

The thermal performance of a flat plate solar collector (FPSC) is a critical indicator that depends on the environment, operational parameters, and dimensions. This study examines the impact of size on thermal performance improvement mechanisms. Firstly, numerical simulation models are introduced as the foundation for optimization research. This involves analyzing the flow resistance of microchannels and defining their structural parameters. Furthermore, experimental tests were conducted on a stainless steel flat plate solar collector (S/S FPSC) with the best design parameters to validate the accuracy of the mathematical model during the design phase. The results indicate that increasing the width of the microchannel and the height of corrugations can effectively enhance the thermal performance of the S/S FPSC. The momentary efficiency is projected to reach a remarkable 86.10% under ideal circumstances. Additionally, a mathematical expression was proposed to establish the relationship between the surrounding conditions and the momentary efficiency of the S/S FPSC. Moreover, the microchannel comprises S/S material, maintaining a homogeneous temperature distribution to maximize heat absorption. The use of stainless steel also extends the lifespan of the FPSC.

Rapid, Massive, and Green Synthesis of Polyoxometalate-Based Metal-Organic Frameworks to Fabricate POMOF/PAN Nanofiber Membranes for Selective Filtration of Cationic Dyes.

Developing high-efficiency membrane materials for the rapid removal of organic dyes is crucial but remains a challenge. Polyoxometalates (POMs) clusters with anionic structures are promising candidates for the removal of cationic dyes via electrostatic interactions. However, their shortcomings, such as their solubility and inability to be mass-produced, hinder their application in water pollution treatment. Here, we propose a simple and green strategy utilizing the room temperature stirring method to mass produce nanoscale polyoxometalate-based metal-organic frameworks (POMOFs) with porous rhomboid-shaped dodecahedral and hexagonal prism structures. The products were labeled as POMOF1 (POMOF-PW12) and POMOF2 (POMOF-PMo12). Subsequently, a series of x wt% POMOF1/PAN (x = 0, 3, 5, and 10) nanofiber membranes (NFMs) were prepared using electrospinning technology, where polyacrylonitrile (PAN) acts as a "glue" molecule facilitating the bonding of POMOF1 nanoparticles. The as-prepared samples were comprehensively characterized and exhibited obvious water stability, as well as rapid selective adsorption filtration performance towards cationic dyes. The 5 wt% POMOF1/PAN NFM possessed the highest removal efficiency of 96.7% for RhB, 95.8% for MB, and 86.4% for CV dyes, which realized the selective separation over 95% of positively charged dyes from the mixed solution. The adsorption mechanism was explained using FT-IR, SEM, Zeta potential, and adsorption kinetics model, which proved that separation was determined via electrostatic interaction, hydrogen bonding, and π-π interactions. Moreover, the POMOF1/PAN membrane presented an outstanding recoverable and stable removal rate after four cycles. This study provides a new direction for the systematic design and manufacture of membrane separation materials with outstanding properties for contaminant removal.

TfR1 mediated iron metabolism dysfunction as a potential therapeutic target for osteoarthritis.

OBJECTIVE: Transferrin receptor-1 (TfR1) plays important roles in controlling cellular iron levels, but its role in OA pathology is unknown. Herein we aim to investigate the role of TfR1 in OA progression and its underlying mechanisms. METHODS: TfR1 expression in cartilage during OA development were examined both in vivo and in vitro. Then IL-1ß was used to induce chondrocytes degeneration in vitro and TfR1 siRNA was used for observing the effect of TfR1 in modulating iron homeostasis, mitochondrial function and degrading enzymes expression. Also the inhibitor of TfR1 was exploited to analyze the protective effect of TfR1 inhibition in vivo. RESULTS: TfR1 is elevated in OA cartilage and contributes to OA inflammation condition. Excess iron not only results in oxidative stress damage and sensitizes chondrocytes to ferroptosis, but also triggers c-GAS/STING-mediated inflammation by promoting mitochondrial destruction and the release of mtDNA. Silencing TfR1 using TfR1 siRNA not only reduced iron content in chondrocytes and inhibited oxidative stress, but also facilitated the mitophagy process and suppressed mtDNA/cGAS/STING-mediated inflammation. Importantly, we also found that Ferstatin II, a novel and selective TfR1 inhibitor, could substantially suppress TfR1 activity both in vivo and in vitro and ameliorated cartilage degeneration. CONCLUSION: Our work demonstrates that TfR1 mediated iron influx plays important roles in chondrocytes degeneration and OA pathogenesis, suggesting that maintaining iron homeostasis through the targeting of TfR1 may represent a novel therapeutic strategy for the treatment of OA.

KRT80 Promotes Lung Adenocarcinoma Progression and Serves as a Substrate for VCP.

Background: Keratin 80(KRT80) encodes a type II intermediate filament protein, known for maintaining cell integrity of cells and its involvement in the tumorigenesis and progression of various cancers. However, comprehensive research on its relevance to lung adenocarcinoma remains limited. Methods: In this study, we utilized multiple databases to investigate the transcriptional expression of KRT80 and its correlation with clinicopathological features. A range of assays, including the Cell Counting Kit 8 assay, colony formation assay, cell migration assay, and flow cytometry, were employed to elucidate the impact of KRT80 on the malignant behavior of lung adenocarcinoma. Immunoprecipitation and mass spectrometry were also used to identify putative genes interacting with KRT80. Results: The expression of KRT80 was elevated in lung adenocarcinoma and patients with high levels of KRT80 expression had poor clinical outcomes. Silencing KRT80 suppressed cell viability, and migration, while overexpression had the opposite effect. In addition, Immunoprecipitation and mass spectrometry revealed an interaction between KRT80 and valosin-containing protein (VCP), with VCP knockdown reducing the stability of KRT80 protein. Overexpression of KRT80 mitigated the inhibitory effect of VCP knockdown to some extent. Conclusion: Our findings collectively suggest that KRT80 is a promising diagnostic and prognostic indicator for lung adenocarcinoma. Additionally, the interaction between KRT80 and VCP plays a crucial role in the progression of lung adenocarcinoma, which implies that KRT80 is a promising therapeutic target.

Prognostic biomarker HIF1α and its correlation with immune infiltration in gliomas.

Certain glioma subtypes, such as glioblastoma multiforme or low-grade glioma, are common malignant intracranial tumors with high rates of relapse and malignant progression even after standard therapy. The overall survival (OS) is poor in patients with gliomas; hence, effective prognostic prediction is crucial. Herein, the present study aimed to explore the potential role of hypoxia-inducible factor 1 subunit alpha (HIF1α) in gliomas and investigate the association between HIF1α and infiltrating immune cells in gliomas. Data from The Cancer Genome Atlas were evaluated via RNA sequencing, clinicopathological, immunological checkpoint, immune infiltration and functional enrichment analyses. Validation of protein abundance was performed using paraffin-embedded samples from patients with glioma. A nomogram model was created to forecast the OS rates at 1, 3 and 5 years after cancer diagnosis. The association between OS and HIF1α expression was estimated using Kaplan-Meier survival analysis and the log-rank test. Finally, HIF1α expression was validated using western blotting, reverse transcription-quantitative PCR, Cell Counting Kit-8 and Transwell assays. The results demonstrated that HIF1α expression was significantly upregulated in gliomas compared with normal human brain glial cells. Immunohistochemistry staining demonstrated differential expression of the HIF1α protein. Moreover, glioma cell viability and migration were inhibited via HIF1α downregulation. HIF1α impacted DNA replication, cell cycling, DNA repair and the immune microenvironment in glioma. HIF1α expression was also positively associated with several types of immune cells and immunological checkpoints and with neutrophils, plasmacytoid dendritic cells and CD56bright cells. The Kaplan-Meier survival analyses further demonstrated a strong association between high HIF1α expression and poor prognosis in patients with glioma. Analysis of the receiver operating characteristic curves demonstrated that HIF1α expression accurately differentiated paired normal brain cells from tumor tissues. Collectively, these findings suggested the potential for HIF1α to be used as a novel prognostic indicator for patients with glioma and that OS prediction models may help in the future to develop effective follow-up and treatment strategies for these patients.

Lifestyle factors and subacromial impingement syndrome of the shoulder: potential associations in finnish participants.

BACKGROUND: Emerging evidence has indicated the associations between subacromial impingement syndrome (SIS) of shoulder and lifestyle factors. However, whether unhealthy lifestyle factors causally increase SIS risk is not determined. This study aims to evaluate whether lifestyle factors are the risk factors of SIS. METHODS: A two-sample Mendelian randomization (MR) study was designed to evaluate the effect of 11 lifestyle factors on SIS risk. Causality was determined using the inverse-variance weighted method to calculate the odds ratio (OR) and establish a 95% confidence interval (CI). Weighted median method, MR-Egger method and MR-PRESSO method were conducted as sensitivity analysis. RESULTS: Four lifestyle factors were identified causally associated with an increased risk of SIS using the IVW method: insomnia (OR: 1.66 95% CI 1.38, 2.00; P = 8.86 × 10- 8), short sleep duration (OR: 1.53 95% CI 1.14, 2.05: P = 0.0043), mobile phone usage (OR: 4.65, 95% CI 1.59, 13.64; P = 0.0051), and heavy manual or physical work (OR: 4.24, 95% CI 2.17, 8.26; P = 2.20 × 10- 5). Another causal but weak association was found between smoking initiation on SIS (OR: 1.17, 95% CI 1.01, 1.35; P = 3.50 × 10- 2). Alcohol, coffee consumption, physical activity, sedentary behavior, sleep duration and computer usage were not found to be causally associated with an increased risk of SIS. Sensitivity analyses indicated that the MR estimates were robust and no heterogeneity and pleiotropy were identified in these MR analyses. CONCLUSION: Sleep habits and shoulder usage were identified as causal factors for SIS. This evidence supports the development of strategies aimed at improving sleep behaviors and optimizing shoulder usage patterns as effective measures to prevent SIS.

A single crystal row-column-array for 3D ultrasound imaging.

In vivo 3D ultrasound imaging with 2D-array transducers is of great importance for both clinical application and biomedical research, but it is complicated in fabrication and also very expensive in hardware due to thousands of electronic channels. In this work, we demonstrate a new fabrication process of 7-MHz 128 + 128 elements row-column-array (RCA) transducer with relaxor ferroelectric PMN-0.28PT single crystal. With piezoelectric single crystal and improved acoustic matching, the optimized performance of -6 dB bandwidth of ∼82 % and insertion loss of -44.6 dB is achieved. The axial and lateral imaging resolutions at different depth of the RCA transducer are quantified by the point spread function (PSF), and the results are respectively 0.20 mm and 0.41 mm at the depth of 7.7 mm, and 0.22 mm and 0.47 mm at the depth of 16.7 mm. The transducer is validated experimentally on a hyperechoic phantom, and 3D view and slices of B-mode images are obtained. The experimental results indicate that our developed RCA transducer can obtain high-quality 3D ultrasound images, demonstrating great potential on ultrafast 3D and functional imaging.

Extensive post-transcriptional regulation revealed by integrative transcriptome and proteome analyses in salicylic acid-induced flowering in duckweed (Lemna gibba).

Duckweed is an aquatic model plant with tremendous potential in industrial and agricultural applications. Duckweed rarely flowers which significantly hinders the resource collection and heterosis utilization. Salicylic acid (SA) can significantly induce duckweed to flower; however, the underlying regulatory mechanisms remain largely unknown. In this work, transcriptome and proteome were conducted in parallel to examine the expression change of genes and proteins in Lemna gibba under SA treatment. A high-quality reference transcriptome was generated using Iso-Seq strategy, yielding 42,281 full-length transcripts. A total of 422, 423, and 417 differentially expressed genes (DEGs), as well as 213, 51, and 92 differentially expressed proteins (DEPs), were identified at flower induction, flower initiation, and flowering stages by ssRNA-seq and iTRAQ methods. Most DEGs and DEPs were only regulated at either the transcriptomic or proteomic level. Additionally, DEPs exhibited low expression correlations with the corresponding mRNAs, suggesting that post-transcriptional regulation plays a pivotal role in SA-induced flowering in L. gibba. Specifically, the genes related to photosynthesis, stress, and hormone metabolism were mainly regulated at the mRNA level, those associated with mitochondrial electron transport / ATP synthesis, nucleotide synthesis, and secondary metabolism were regulated at the protein level, while those related to redox metabolism were regulated at the mRNA and/or protein levels. The post-transcriptional regulation of genes relevant to hormone synthesis, transcription factors, and flowering was also extensively analyzed and discussed. This is the first study of integrative transcriptomic and proteomic analyses in duckweed, providing novel insights of post-transcriptional regulation in SA-induced flowering of L. gibba.

Hydrogen Production through Distinctive C-C Cleavage during Acetic Acid Reforming at Low Temperature.

Acetic acid reforming is a green method for sustainable hydrogen production owing to its renewable source from biomass conversion. However, conventional acetic acid reforming would produce various byproducts, including CO, CH4 and so on. Here, we develop a distinctive method for selective hydrogen production from C-C directional cleavage during acetic acid reforming. Completely different from conventional acetic acid reforming process, acetic acid would react with water over organoruthenium catalyst during its C-C cleavage at low temperature, then produce methanol and formic acid (CH3 COOH+H2 O→CH3 OH+HCOOH). Lastly, methanol and formic acid could further decompose into hydrogen and carbon dioxide over organoruthenium selectively. As a result, there is little CO and CH4 produced in the first step of C-C bond cleavage during acetic acid reforming at 100 °C. Hydrogen production rate is up to 26.8 molH2 /(h-1 *mol-1 Ru ) at 150 °C through a tandem catalysis. A mechanism for C-C cleavage of acetic acid is proposed based on intermediate product analysis and density functional theory (DFT) calculation. Firstly, the C-C single bond was transformed into C=C double bond by dropping one H atom to organoruthenium. Then the coming H2 O molecule reacted with the C=C bond by an addition reaction, forming methanol and formic acid. This research not only proposes distinctive reaction pathway for hydrogen production from acetic acid reforming, but also provides some inspiration for selective C-C bond cleavage during ethanol reforming.

Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure-Activity Relationship Model.

The quantitative structure-activity relationship (QSAR) is one of the most popular methods for the virtual screening of new drug leads and optimization. Herein, we collected a dataset of 955 MIC values of pleuromutilin derivatives to construct a 2D-QSAR model with an accuracy of 80% and a 3D-QSAR model with a non-cross-validated correlation coefficient (r2) of 0.9836 and a cross-validated correlation coefficient (q2) of 0.7986. Based on the obtained QSAR models, we designed and synthesized pleuromutilin compounds 1 and 2 with thiol-functionalized side chains. Compound 1 displayed the highest antimicrobial activity against both Staphylococcus aureus ATCC 29213 (S. aureus) and Methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentrations (MICs) < 0.0625 µg/mL. These experimental results confirmed that the 2D and 3D-QSAR models displayed a high accuracy of the prediction function for the discovery of lead compounds from pleuromutilin derivatives.

Genetic evidence suggests a genetic association between major depressive disorder and reduced cortical gray matter volume: A Mendelian randomization study and mediation analysis.

BACKGROUND: Several studies have suggested an association between major depressive disorder (MDD) and abnormal brain structure. However, it is unclear whether MDD affects cortical gray matter volume, a common indicator of cognitive function. We aimed to determine whether MDD was associated with decreased cortical gray matter volume (GMV) through a Mendelian randomization (MR) study. METHODS: We obtained summary genetic data from a study conducted by the Psychiatric Genomics Consortium, which recruited a total of 480,359 participants (135,458 cases and 344,901 controls). Genetic tools-single nucleotide polymorphisms (SNPs)-of MDD were extracted from the study and their effects on gray matter volumes of the cortex and total brain were evaluated in a large cohort from the UK Biobank (n = 8427). The effects of the SNPs were pooled using inverse variance weighted (IVW) analysis and further tested in several sensitivity analyses. We tested whether C-reactive protein (CRP) levels and interleukin-6 signaling were the mediators of the effects using a multivariate MR model. RESULTS: Thirty-three SNPs were identified and adopted as genetic tools for predicting MDD. IVW analysis showed that MDD was associated with lower overall GMV (beta value -0.106, 95%CI -0.188 to -0.023, p = 0.011) in the frontal pole (left frontal pole, -0.152, 95%CI -0.177 to -0.127, p = 0.013; right frontal pole, -0.133, 95%CI -0.253 to -0.013, p = 0.028). Multivariate and mediation analysis showed that interleukin-6 was an important mediator of GMV reduction. Reverse causality analysis found no evidence that total GMV affected the risk of MDD, but showed that increased left precuneus cortex volume and left posterior cingulate cortex volume were associated with increased risk of MDD. LIMITATIONS: Potential pleiotropic effects and overestimation of real-world effects. Key assumptions for MR analysis may not be satisfactorily met. CONCLUSION: MDD was associated with a reduced GMV, and interleukin-6 might be a mediator of GMV reduction.

Aromatic and magnetic properties in a series of heavy rare earth-doped Ge6 cluster anions.

A series of pentagonal bipyramidal anionic germanium clusters doped with heavy rare earth elements, REGe 6 - (RE = Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu), have been identified at the PBE0/def2-TZVP level using density functional theory (DFT). Our findings reveal that the centrally doped pentagonal ring structure demonstrates enhanced stability and heightened aromaticity due to its uniform bonding characteristics and a larger charge transfer region. Through natural population analysis and spin density diagrams, we observed a monotonic decrease in the magnetic moment from Gd to Yb. This is attributed to the decreasing number of unpaired electrons in the 4f orbitals of the heavy rare earth atoms. Interestingly, the system doped with Er atoms showed lower stability and anti-aromaticity, likely due to the involvement of the 4f orbitals in bonding. Conversely, the systems doped with Gd and Tb atoms stood out for their high magnetism and stability, making them potential building blocks for rare earth-doped semiconductor materials.

METTL3-mediated HSPA9 m6A modification promotes malignant transformation and inhibits cellular senescence by regulating exosomal mortalin protein in cervical cancer.

The role of RNA methyltransferase 3 (METTL3) in tumor progression when tethered to aberrantly expressed oncogenes remains unknown. In especial, the correlation between cervical cancer (CCa)-derived exosomes and m6A methylation in malignant traits of cervical epithelium is currently elusive. Mortalin expression was found to be up-regulated in plasma exosomes isolated from CCa patients. Furthermore, mortalin gained increased mRNA stability and enhanced translation efficiency via the m6A methylation in the HSPA9 mRNA 3'UTR, which was catalysed by METTL3 in CCa cells. Exosomal mortalin overexpression significantly promoted the proliferation, migration and invasion of CCa both in vitro and in vivo. Additionally, exosome-encapsulated mortalin suppressed cellular senescence and facilitated malignant transformation by blocking nuclear transport of p53, thereby preventing the p53-Gadd45A interaction and resulting in inactivation of p53. Our studies demonstrated the significant role of METTL3 mediated exosomal mortalin in malignant transformation and cellular senescence suppression of CCa. Exosomal mortalin could clinically serve as a potential early-diagnosis biomarker and therapeutic target for CCa given its abundance and propensity to be found.

Nonreciprocal optomechanically induced transparency and enhanced ground-state cooling in a reversed-dissipation cavity system.

We explore the prospects of phase-modulated optical nonreciprocity and enhanced ground-state cooling of a mechanical resonator for the reversed-dissipation system, where the dissipative coupling between two cavities is realized through the adiabatic elimination of a low-Q mechanical mode, while a high-Q mechanical mode interacts with two mutually coupled cavities, forming a closed-loop structure. This unique system facilitates the nontrivial phenomenon of optomechanically induced transparency (OMIT), which exhibits asymmetry due to the frequency shift effect. We also observe the emergence of parity-dependent unidirectional OMIT windows (appearing under the phase-matching condition), which can be dynamically modulated by both the phase factors and the strength of the dissipative coupling. Furthermore, our study delves into the ground-state cooling effect operating within the reversed-dissipation regime. Intriguingly, the cooling effect can be significantly enhanced by carefully engineering dissipative complex coupling, such as in the phase-matching condition. The potential applications of this scheme extend to the fabrication of ideal optical isolators in optical communication systems and the manipulation of macroscopic mechanical resonators at the quantum level, presenting exciting opportunities in quantum technologies.

Exploring the stability and aromaticity of rare earth doped tin cluster MSn16- (M = Sc, Y, La).

Rare earth elements have high chemical reactivity, and doping them into semiconductor clusters can induce novel physicochemical properties. The study of the physicochemical mechanisms of interactions between rare earth and tin atoms will enhance our understanding of rare earth functional materials from a microscopic perspective. Hence, the structure, electronic characteristics, stability, and aromaticity of endohedral cages MSn16- (M = Sc, Y, La) have been investigated using a combination of the hybrid PBE0 functional, stochastic kicking, and artificial bee colony global search technology. By comparing the simulated results with experimental photoelectron spectra, it is determined that the most stable structure of these clusters is the Frank-Kasper polyhedron. The doping of atoms has a minimal influence on density of states of the pure tin system, except for causing a widening of the energy gap. Various methods such as ab initio molecular dynamics simulations, the spherical jellium model, adaptive natural density partitioning, localized orbital locator, and electron density difference are employed to analyze the stability of these clusters. The aromaticity of the clusters is examined using iso-chemical shielding surfaces and the gauge-including magnetically induced currents. This study demonstrates that the stability and aromaticity of a tin cage can be systematically adjusted through doping.

Anisotropic Charge Migration on Perovskite Oxysulfide for Boosting Photocatalytic Overall Water Splitting.

The synthesis of photocatalysts with both broad light absorption and efficient charge separation is significant for a high solar energy conversion, which still remains to be a challenge. Herein, a narrow-bandgap Y2Ti2O5S2 (YTOS) oxysulfide nanosheet coexposed with defined {101} and {001} facets synthesized by a flux-assisted solid-state reaction was revealed to display the character of an anisotropic charge migration. The selective photodeposition of cocatalysts demonstrated that the {101} and {001} surfaces of YTOS nanosheets were the reduction and oxidation regions during photocatalysis, respectively. Density functional theory (DFT) calculations indicated a band energy level difference between the {101} and {001} facets of YTOS, which contributes to the anisotropic charge migration between them. The exposed Ti atoms on the {101} surface and S atoms on the {001} surface were identified, respectively, as reducing and oxidizing centers of YTOS nanosheets. This anisotropic charge migration generated a built-in electric field between these two facets, quantified by spatially resolved surface photovoltage microscopy, the intensity of which was found to be highly correlated with photocatalytic H2 production activity of YTOS, especially exhibiting a high apparent quantum yield of 18.2% (420 nm) after on-site modification of a Pt@Au cocatalyst assisted by Na2S-Na2SO3 hole scavengers. In conjunction with an oxygen-production photocatalyst and a [Co(bpy)3]2+/3+ redox shuttle, the YTOS nanosheets achieved a solar-to-hydrogen conversion efficiency of 0.15% via a Z-scheme overall water splitting. Our work is the first to confirm anisotropic charge migration in a perovskite oxysulfide photocatalyst, which is crucial for enhancing charge separation and surface catalytic efficiency in this material.

Optogenetic activation of the lateral habenulaD1R-ventral tegmental area circuit induces depression-like behavior in mice.

A number of different receptors are distributed in glutamatergic neurons of the lateral habenula (LHb). These glutamatergic neurons are involved in different neural pathways, which may identify how the LHb regulates various physiological functions. However, the role of dopamine D1 receptor (D1R)-expressing habenular neurons projecting to the ventral tegmental area (VTA) (LHbD1R-VTA) remains not well understood. In the current study, to determine the activity of D1R-expressing neurons in LHb, D1R-Cre mice were used to establish the chronic restraint stress (CRS) depression model. Adeno-associated virus was injected into bilateral LHb in D1R-Cre mice to examine whether optogenetic activation of the LHb D1R-expressing neurons and their projections could induce depression-like behavior. Optical fibers were implanted in the LHb and VTA, respectively. To investigate whether optogenetic inhibition of the LHbD1R-VTA circuit could produce antidepressant-like effects, the adeno-associated virus was injected into the bilateral LHb in the D1R-Cre CRS model, and optical fibers were implanted in the bilateral VTA. The D1R-expressing neuronal activity in the LHb was increased in the CRS depression model. Optogenetic activation of the D1R-expressing neurons in LHb induced behavioral despair and anhedonia, which could also be induced by activation of the LHbD1R-VTA axons. Conversely, optogenetic inhibition of the LHbD1R-VTA circuit improved behavioral despair and anhedonia in the CRS depression model. D1R-expressing glutamatergic neurons in the LHb and their projections to the VTA are involved in the occurrence and regulation of depressive-like behavior.

MFG-E8 facilitates heart repair through M1/M2 polarization after myocardial infarction by inhibiting CaMKII.

BACKGROUND: M1/M2 macrophage polarization affects patient outcomes after myocardial infarction (MI). The relationship between milk fat globule-epidermal growth factor 8 (MFG-E8) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) on macrophage polarization after MI is unknown. To investigate the functional role of MFG-E8 in modulating cardiac M1/M2 macrophage polarization after MI, especially its influence on CaMKII signaling. METHODS: Human ventricular tissue and blood were obtained from patients with MI and controls. MFG-E8-KO mice were constructed (C57BL/6). The mice were randomized to WT-sham, sham-MFG-E8-KO, WT-PBS, rmMFG-E8 (WT injected with rmMFG-E8 10 min after MI), and MFG-E8-KO. The mouse macrophage cell line RAW264.7 was obtained. CaMKII, p-CaMKII, Akt, and NF-κB p65 were determined by qRT-PCR, western blot, and immunofluorescence. RESULTS: The MFG-E8 levels were significantly enhanced after MI in the hearts and plasma of patients with MI compared with controls. The MFG-E8 levels were significantly increased in the hearts and plasma of mice after MI. MFG-E8 was derived from cardiac fibroblasts. The administration of rmMFG-E8 improved ventricular remodeling and cardiac function after MI. rmMFG-E8 did not suppress infiltrating monocyte/macrophages into the peri-infarct area. rmMFG-E8 suppressed the polarization of macrophages to the M1 phenotype and promoted the polarization of macrophages to the M2 phenotype. rmMFG-E8 suppressed CaMKII-dependent signaling in macrophages. CONCLUSIONS: MFG-E8 and CaMKII appear to collaboratively regulate myocardial remodeling and M1/M2 macrophage polarization after MI. These observations suggest new roles for MFG-E8 in inhibiting M1 but promoting M2 macrophage polarization.