A differentiation roadmap of murine placentation at single-cell resolution.

The placenta is one of the most important yet least understood organs. Due to the limitations of conventional research approaches, we are still far from a comprehensive understanding of mouse placentation, especially regarding the differentiation of trophoblast lineages at the early developmental stage. To decipher cell compositions and developmental processes, we systematically profile the single-cell transcriptomes of trophoblast cells from extraembryonic tissues (embryonic day 7.5 (E7.5) and E8.5) and placentae (E9.5-E14.5) at one-day intervals. We identify distinct trophoblast cell types during mouse placentation, including unreported progenitor cells and intermediate precursor cells. An updated differentiation roadmap of mouse trophoblast lineages is presented following systematic transcriptome analyses. Based on transcriptomic regulatory network inference, we specify transcription factors responsible for the regulation of dynamic developmental processes during lineage diversification. We map lineage differentiation trajectories and find that sinusoid trophoblast giant cells arise from the subpopulation of ectoplacental cone cells. We provide a comprehensive single-cell data resource to shed light on future mechanistic studies of the gene regulatory networks governing hemochorial placentation.

Information set supported deep learning architectures for improving noisy image classification.

Deep learning models have been widely used in many supervised learning applications. However, these models suffer from overfitting due to various types of uncertainty with deteriorating performance when facing data biases, class imbalance, or noise propagation. The Information-Set Deep learning (ISDL) architectures with four variants are developed by integrating information set theory and deep learning principles to address the critical problem of the absence of robust deep learning models. There is a description of the ISDL architectures, learning algorithms, and analytic workflows. The performance of the ISDL models and standard architectures is evaluated using a noise-corrupted benchmark dataset. The experimental results show that the ISDL models can efficiently handle noise-dominated uncertainty and outperform peer architectures.

An Optimizing Surgical Procedures for Correcting Severe Constricted Ears: Helix Costal Cartilage Scaffold Combined With V-Y Advanced Flap.

PURPOSE: A constricted ear is a deformity that is distinguished by curling of the upper portion of the ear, which includes the helix, scapha, and antihelix. The treatment for severely constricted ears seems to be quite invasive. To reduce invasiveness and fully utilize the folded cartilage, the authors used a helix costal cartilage scaffold combined with a single V-Y advanced flap in the correction of Tanzer type IIB constricted ear deformity to investigate the clinical effect. MATERIALS AND METHODS: From 2020 to 2021, autologous costal cartilage helix stent combined with local V-Y advanced flap was applied to correct the constricted ear malformation in 18 patients admitted to the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences. RESULTS: All patients were followed for a duration of 6 to 12 months (average 7 months). Reconstructed auricles were cosmetically satisfying, with a natural-looking helix and enlarged cavum conchae cavity, as well as auricle sizes that were close to normal and near symmetry between both ears. CONCLUSIONS: With satisfactory clinical results, our technique can be used to repair types IIB cup ear deformities. It has a broad range of practical applications.

Sequential KOtBu/FeCl3-catalyzed reductive phosphonylation of tertiary amides for the synthesis of α-amino phosphonates and phosphines.

A simple, mild and efficient sequential KOtBu/FeCl3-catalyzed reductive phosphonylation of tertiary amides is herein described. This process first involved the KOtBu-catalyzed selective semi-reduction of tertiary amides to hemiaminal intermediates by TMDS (1,1,3,3-tetramethyldisiloxane) and then the FeCl3-catalyzed nucleophilic addition of the hemiaminal intermediates to phosphonates, which allowed the straightforward synthesis of α-amino phosphonates in moderate to good yields. This method applied well to amides and lactams that bear no strong acidic α-hydrogens, and various functional groups, including methoxy, methylthio, cyano, halogen, and heterocycles, could be tolerated.

Two new indole alkaloids from Nauclea officinalis and their evaluation for cytotoxic activities.

Two new indole alkaloids, naucleamide H (1) and (±)-19-O-butylangustoline (8), along with seven known alkaloids, 3,14-dihydroangustine (2), (-)-naucleofficine D (3a), (+)-naucleofficine D (3b), nauclefine (4), angustidine (5),19-O-ethylangustoline (6) and angustine (7) were isolated from the water extract of Nauclea officinalis. The structures of these compounds were established by spectroscopic analysis. Among them, the cytotoxicity of 1, 2, 6 and 8 were evaluated against six human cancer cell lines (HepG-2, SKOV3, HeLa, SGC 7901, MCF-7 and KB) in vitro for the first time with 5-fluorouracil as a positive control drug. The new compound 1 had a strong inhibitory effect on the proliferation of HepG-2 with an IC50 value of 19.59 µg/mL. The new compound 8 had a strong inhibitory effect on HepG-2, SKOV3, HeLa, MCF-7 and KB, IC50 value was 5.530, 23.11, 31.30, 32.42 and 37.26 µg/mL, respectively.

Removing unreacted amino groups in graphitic carbon nitride through residual heating to improve the photocatalytic performance.

In most of the research about graphitic carbon nitride (g-C3N4), g-C3N4 is prepared through the calcination of nitrogen-rich precursors. However, such a preparation method is time-consuming, and the photocatalytic performance of pristine g-C3N4 is lackluster due to the unreacted amino groups on the surface of g-C3N4. Therefore, a modified preparation method, calcination through residual heating, was developed to achieve rapid preparation and thermal exfoliation of g-C3N4 simultaneously. Compared with pristine g-C3N4, the samples prepared by residual heating had fewer residual amino groups, a thinner 2D structure, and higher crystallinity, which led to a better photocatalytic performance. The photocatalytic degradation rate of the optimal sample for rhodamine B could reach 7.8 times higher than that of pristine g-C3N4.

Frequent EGFR exon 20 insertion in the so-called peripheral-type squamous cell neoplasm of uncertain malignant potential: a variant of bronchiolar adenoma or under-recognised entity?

INTRODUCTION: Herein we describe a series of rare peripheral pulmonary neoplasms temporarily termed "peripheral type squamous cell neoplasm of uncertain malignant potential (PSCN-UMP)" and investigate their relationship to bronchiolar adenoma (BA) and squamous cell carcinoma (SCC). MATERIALS AND METHODS: The histologic and immunohistochemical features of 10 PSCN-UMPs and six BAs were compared. Whole exome sequencing (WES) and bioinformatics analysis were performed to further compare the genetic features of PSCN-UMPs, BAs, and NSCLCs. RESULTS: All PSCN-UMPs were peripherally located and histologically characterised by the lepidic, nested, and papillary proliferation of relatively bland squamous cells, accompanied by entrapped hyperplastic reactive pneumocytes. The basal squamous cells coexpressed TTF1 and squamous markers. Both cellular components exhibited bland morphology and a low proliferative activity. The six BAs met the morphologic and immunophenotypic features of proximal-type BA. Genetically, driver mutations, including frequent EGFR exon 20 insertions, were found in PSCN-UMPs, while the KRAS mutation, BRAF mutation, and ERC1::RET fusion were detected in BAs. PSCN-UMPs also shared some alterations with BAs in mutational signatures, while copy number variants (CNV) were enriched in MET and NKX2-1 in PSCN-UMP and MCL1, MECOM, SGK1, and PRKAR1A in BA. CONCLUSION: PSCN-UMPs exhibited the proliferation of bland squamous cells accompanied by entrapped pneumocytes and frequent EGFR exon 20 insertions, which showed distinct features from BAs and SCCs. Recognition of this specific entity will help to expand the morphologic and molecular spectrum of peripheral lung squamous neoplasms.

Comparative study of first-principles approaches for effective Coulomb interaction strength Ueff between localized f-electrons: Lanthanide metals as an example.

As correlation strength has a key influence on the simulation of strongly correlated materials, many approaches have been proposed to obtain the parameter using first-principles calculations. However, a comparison of the different Coulomb strengths obtained using these approaches and an investigation of the mechanisms behind them are still needed. Taking lanthanide metals as an example, we research the factors that affect the effective Coulomb interaction strength, Ueff, by local screened Coulomb correction (LSCC), linear response (LR), and constrained random-phase approximation (cRPA) in the Vienna Ab initio Simulation Package. The Ueff LSCC value increases from 4.75 to 7.78 eV, Ueff LR is almost stable at about 6.0 eV (except for Eu, Er, and Yb), and Ueff cRPA shows a two-stage decreasing trend in both light and heavy lanthanides. To investigate these differences, we establish a scheme to analyze the coexistence and competition between the orbital localization and the screening effect. We find that LSCC and cRPA are dominated by the orbital localization and the screening effect, respectively, whereas LR shows the balance of the competition between the two factors. Additionally, the performance of these approaches is influenced by different starting points from the Perdew-Burke-Ernzerhof (PBE) and PBE + U, especially for cRPA. Our results provide useful knowledge for understanding the Ueff of lanthanide materials, and similar analyses can also be used in the research of other correlation strength simulation approaches.

Time-dependent band position difference between vibrational sum and difference frequency generation: a phenomenon originating from dispersion in the visible pulse.

Vibrational spectroscopy is significant for identifying chemical specification. Here, the spectral band frequencies corresponding to the same molecular vibration in sum frequency generation (SFG) and difference frequency generation (DFG) spectra present delay-dependent deviation. Through numerical analysis of time resolved SFG and DFG spectra with a frequency marker in the incident IR pulse, the frequency ambiguity was not caused by any structure and dynamic variation on the surface, but from the dispersion in the incident visible pulse. Our results provide a helpful method to correct the vibrational frequency deviation and improve the assignment accuracy for SFG and DFG spectroscopies.

The impact of key monitoring policy on the usage of policy-related drugs in Hubei Province, China.

Introduction: This study evaluated quantitatively the impact of the first batch of the catalog of Key Monitoring and Rational Use Drugs (KMRUD) in Hubei Province on policy-related drug use and expenditures. Methods: This study is aimed to provide a basis for the successful implementation of subsequent catalogs of KMRUD, which may promote the standardization of clinical application of related drugs and effectively reduce drug expenses of the patients. Data on the procurement records of policy-related drugs from January 2018 to June 2021 were obtained from the Drug Centralized Procurement Platform of the Public Resources Trading Center in Hubei Province. Interrupted time-series (ITS) analysis was used in this study. Results: After the implementation of the first batch of the catalog of KMRUD, the consumption of policy-related drugs decreased by 83.29% in 2020. The spending on policy-related drugs decreased by 83.93% in 2020. The introduction of the first batch of the catalog of KMRUD was associated with a significant decrease in the spending on policy-related drugs in the level (p = 0.001). Before the implementation of the KMRUD catalog policy, the Defined Daily Doses (DDDs) (ß1 = -32.26 p < 0.001) and spending (ß1 = -3662.19 p < 0.001) on policy-related drugs showed a downward trend. In the aggregated ITS analysis, the Defined Daily Dose cost (DDDc) of policy-related drugs decreased significantly in the trend (p < 0.001). After the implementation of the KMRUD catalog policy, the monthly procurement volume of 10 policy-related drugs have a significant downward trend (p < 0.05), and 4 policy-related drugs have a significant upward trend (p < 0.05). Conclusion: After the policy intervention, the total DDDc on policy-related drugs indicated sustained reductions. The KMRUD policy overall achieved the goal of limiting policy-related drug use and controlling cost increases. And it is recommended that the health department quantify the usage indicator of adjuvant drugs, uniform standards, and apply prescription reviews and dynamic supervision, and other measures to strengthen supervision.

Malignant pleural effusion diagnosis and therapy.

Malignant pleural effusion (MPE) is a serious complication of advanced tumor, with relatively high morbidity and mortality rates, and can severely affect the quality of life and survival of patients. The mechanisms of MPE development are not well defined, but much research has been conducted to gain a deeper understanding of this process. In recent decades, although great progress has been made in the management of MPE, the diagnosis and treatment of MPE are still major challenges for clinicians. In this article, we provide a review of the research advances in the mechanisms of MPE development, diagnosis and treatment approaches. We aim to offer clinicians an overview of the latest evidence on the management of MPE, which should be individualized to provide comprehensive interventions for patients in accordance with their wishes, health status, prognosis and other factors.

Flexible Quantum Dot Light-Emitting Device for Emerging Multifunctional and Smart Applications.

Quantum dot light-emitting diodes (QLEDs), owing to their exceptional performances in device efficiency, color purity/tunability in the visible region, and solution-processing ability on various substrates, become a potential candidate for flexible and ultrathin electroluminescent (EL) lighting and display. Moreover, beyond the lighting and display, flexible QLEDs are enabled with endless possibilities in the era of the internet of things and artificial intelligence by acting as input/output ports in wearable integrated systems. Challenges remain in the development of flexible QLEDs with the goals for high performance, excellent flexibility/even stretchability, and emerging applications. In this paper, we review the recent developments of QLEDs including quantum dot materials, working mechanism, flexible/stretchable strategies, and patterning strategies, and highlight its emerging multifunctional integrations and smart applications covering wearable optical medical devices, pressure-sensing EL devices, and neural smart EL devices. We also summarize the remaining challenges and make an outlook on the future development of flexible QLEDs. The review is expected to offer a systematic understanding and valuable inspiration for flexible QLEDs to simultaneously satisfy optoelectronic and flexible properties for emerging applications. This article is protected by copyright. All rights reserved.

miR-27a-3p relieves heat stress-induced mitochondrial damage and aberrant milk protein synthesis through MEK/ERK pathway in BMECs.

With global warming, heat stress has become a primary factor that compromises the health and milk quality of dairy cows. Here, we investigated the function and underlying regulatory mechanism of miR-27a-3p in bovine mammary epithelial cells (BMECs) under heat-stress conditions. The current study showed that miR-27a-3p could prevent heat stress-induced BMEC oxidative stress and mitochondrial damage by regulating the balance between mitochondrial fission and fusion processes. Importantly, we found that miR-27a-3p could increase cell proliferation under heat stress conditions by regulating the MEK/ERK pathway and cyclin D1/E1. Interestingly, miR-27a-3p is also involved in the regulation of milk protein synthesis-related protein expression, such as CSN2 and ELF5. Inhibition of the MEK/ERK signaling pathway by AZD6244 blocked the regulatory function of miR-27a-3p in cell proliferation and milk protein synthesis in BMECs under heat stress conditions. Our findings demonstrated that miR-27a-3p protects BMECs from heat stress-induced oxidative stress and mitochondrial damage through the MEK/ERK pathway, thereby promoting BMECs proliferation and lactation in dairy cows. The potential regulatory mechanism of miR-27a-3p in attenuating heat stress-induced apoptosis and lactation defect in BMECs.

Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex.

Neuroinflammation is tightly associated with onset of depression. The nuclear receptor related 1 protein (Nurr1, also called Nr4a2), its roles in dopaminergic neurons is well understood, which can alleviate inflammation. Nevertheless, potential effects of Nr4a2 on neuroinflammation associated with depression still remains unclear. Chronic lipopolysaccharides (LPS) stress induced depressive-behaviors were confirmed via behavioral tests. Differentially expressed genes were detected by using RNA-sequencing. The anterior cingulate cortex (ACC) tissues were collected for biochemical experiments. The Golgi-Cox staining and virus labeling were used to evaluate the dendritic spines. We applied fluoxetine (FLX) and amodiaquine dihydrochloride (AQ, a highly selective agonist of Nr4a2) in mice. Overexpression experiments were performed by injecting with AAV-Nr4a2-EGFP into ACC. Chemogenetic activation of CamkII neurons via injecting the hM3Dq virus. Mice treated with LPS displayed depressive- and anxiety-like behaviors. The reduction of Nr4a2 and FosB induced by LPS were rescued by pretreatment with FLX or AQ. More importantly, LPS-induced behavior deficits in mice were also alleviated via fluoxetine treatment and pharmacological activation the expression of Nr4a2. Meanwhile, enhancing the level of Nr4a2 could improve dendritic spines loss of neuron and morphological changes in microglia. Overexpression of Nr4a2 in ACC reversed the depressive- and anxiety-like behaviors caused by LPS administration. Activation of CamkII neurons in ACC could robustly increase the expression of Nr4a2 and improve LPS-induced behavior deficits. Our findings demonstrate that the Nr4a2 may regulate depressive-like behaviors via alleviating the impairment of morphology and function on microglia and CamkII neurons induced by chronic neuroinflammation.

Polystyrene microplastics-induced macrophage extracellular traps contributes to liver fibrotic injury by activating ROS/TGF-ß/Smad2/3 signaling axis.

Microplastics (MPs) are a type of emerging pollutant, posing a great threat to human and animal health. While recent studies have revealed the link between MPs exposure and liver injury of organisms, the effect of particle size on the level of MPs-induced hepatotoxicity and the intrinsic mechanism remain to be explored. Here, we established a mouse model exposed to two-diameter polystyrene MPs (PS-MPs, 1-10 µm or 50-100 µm) for 30 days. The in vivo results revealed that PS-MPs caused liver fibrotic injury in mice, accompanied with macrophages recruitment and macrophage extracellular traps (METs) formation, which were negatively correlated with particle size. The data in vitro showed that PS-MPs treatment could induce macrophages to release METs in a reactive oxygen species (ROS)-independent manner, and the METs formation level caused by large-size particles was higher than small-size particles. Further mechanistic analysis of a cell co-culture system revealed that PS-MPs-induced METs release led to a hepatocellular inflammatory response and epithelial-mesenchymal transition (EMT) via activating the ROS/TGF-ß/Smad2/3 signaling axis, and this biological crosstalk could be relieved by DNase I. Overall, this findings demonstrates the key role of the action mechanism of METs in aggravating MPs-caused liver injury.

View of Times and Temporal Focus under the Pace of Life on the Impact of Intertemporal Decision Making.

Previous studies have explored the effects of time poverty and money worship on intertemporal decision making based on a resource scarcity perspective. However, how the pace of life affects intertemporal decision making has not been examined. Furthermore, manipulating time perceptions can influence intertemporal decision-making preferences. Based on the perspective of time perception differences, it remains unknown how views of time or temporal focus affect the intertemporal decision making of individuals with different pace of life. To address these issues, study 1 adopted a correlational study to initially explore the relationship between the pace of life and intertemporal decision making. Studies 2 and 3 used manipulation experiments to examine the effects of the pace of life and view of time and temporal focus and pace of life on intertemporal decision making. The results suggest that the faster the life pace, the more recent rewards are preferred. Views of time and temporal focus manipulations can influence the intertemporal decision making of faster-paced individuals, making them prefer smaller-sooner (SS) payoffs under a linear view of time or future temporal focus and larger-later (LL) payoffs under a circular view of time or past temporal focus. However, the manipulation does not affect the intertemporal decision of slower-paced individuals. Our study examined the effect of the pace of life on intertemporal decision making based on a resource scarcity perspective, and found boundary conditions for the influence of the view of time and temporal focus on intertemporal decision making based on the perspective of differences in people's perception of time.

Precisely Slight Regulation of Emission Maxima and Construction of Highly Efficient Electroluminescent Materials with High Color Purity.

Advanced multiple resonance induced thermally activated delayed fluorescence (MR-TADF) emitters have emerged as a privileged motif for applications in organic light-emitting diodes (OLEDs), because they furnish highly tunable bandgap with emission ranges spanning the visible light region, and have the intrinsic properties of outstanding TADF characteristics and high color purity emission. One of the typical construction paradigms of MR-TADF molecule is based on polycyclization of MR parent core and a representative target model molecule BN-TP has been prepared. Herein, based on the unique nitrogen-atom embedding molecular engineering (NEME) strategy, a series of congeners of BN-TP, namely BN-TP-Nx (x = 1, 2, 3, 4), have been customized. The nitrogen-atom anchored at different position of triphenylene hexagonal lattice entails varying degrees of perturbation to the electronic structure. The newly-constructed emitters have demonstrated the precisely slight regulation of emission maxima of MR-TADF emitters to meet the actual industrial demand, and further enormously enriched the MR-TADF molecular reservoir. The BN-TP-N3-based OLED exhibits ultrapure green emission, with peak of 524 nm, full-width at half-maximum (FWHM) of 33 nm, Commission Internationale de L'Eclairage (CIE) coordinates of (0.23, 0.71), and maximum external quantum efficiency (EQE) of 37.3%.

Knowledge Mapping of Intracranial Aneurysm Clipping: A Bibliometric and Visualized Study (2001-2021).

BACKGROUND: Intracranial aneurysms (IAs) are common cerebrovascular diseases with high rates of mortality and disability. With the development of endovascular treatment technologies, the treatment of intracranial aneurysms has gradually turned to endovascular treatment. However, due to the complex disease characteristics and technical challenges of intracranial aneurysm treatment, surgical clipping still plays an important role. However, there is no summary of the research status and future trends in IA clipping. METHOD: Publications related to IA clipping from 2001 to 2021 were retrieved from the Web of Science Core Collection (WoSCC) database. We conducted a bibliometric analysis and visualized study with the help of VOSviewer software and R program. RESULTS: We included 4104 articles from 90 countries. The volume of publications on IA clipping has generally increased. The United States, Japan and China were the countries that contributed the most. The University of California, San Francisco, Mayo Clinic, and the Barrow Neurological Institute are the main research institutions. World Neurosurgery and the Journal of Neurosurgery were the most popular journal and the most co-cited journal, respectively. These publications come from 12,506 authors among which Lawton MT, Spetzler RF, and Hernesniemi J published the most papers. Studies from the past 21 years on IA clipping can generally be divided into five parts: (1) the characteristics and technical difficulties of IA clipping; (2) perioperative management and imaging evaluation of IA clipping; (3) risk factors for subarachnoid hemorrhage caused by rupture of IA clippings; (4) outcomes, prognosis, and related clinical trials of IA clipping; and (5) endovascular management for IA clipping. "Occlusion," "experience," "internal carotid-artery," "intracranial anurysms," "management," and "subarachnoid hemorrhage" are the major keywords for future research hotspots. CONCLUSION: This bibliometric study clarified the global research status of IA clipping between 2001 and 2021. The United States contributed the most publications and citations, and World Neurosurgery and Journal of Neurosurgery can be considered landmark journals in this field. Studies regarding occlusion, experience, management, and subarachnoid hemorrhage will be the next research hotspots related to IA clipping in the future.

The clinical and neurocognitive functional changes with awake brain mapping for gliomas invading eloquent areas: Institutional experience and the utility of The Montreal Cognitive Assessment.

Objective: Awake craniotomy with intraoperative brain functional mapping effectively reduces the potential risk of neurological deficits in patients with glioma invading the eloquent areas. However, glioma patients frequently present with impaired neurocognitive function. The present study aimed to investigate the neurocognitive and functional outcomes of glioma patients after awake brain mapping and assess the experience of a tertiary neurosurgical center in China over eight years. Methods: This retrospective study included 80 patients who underwent awake brain mapping for gliomas invading the eloquent cortex between January 2013 and December 2021. Clinical and surgical factors, such as the extent of resection (EOR), perioperative Karnofsky Performance Score (KPS), progression-free survival (PFS), and overall survival (OS), were evaluated. We also used the Montreal Cognitive Assessment (MoCA) to assess the neurocognitive status changes. Results: The most frequently observed location of glioma was the frontal lobe (33/80, 41.25%), whereas the tumor primarily invaded the language-related cortex (36/80, 45%). Most patients had supratotal resection (11/80, 13.75%) and total resection (45/80, 56.25%). The median PFS was 43.2 months, and the median OS was 48.9 months in our cohort. The transient (less than seven days) neurological deficit rate was 17.5%, whereas the rate of persistent deficit (lasting for three months) was 15%. At three months of follow-up, most patients (72/80, 90%) had KPS scores > 80. Meanwhile, compared to the preoperative baseline tests, the changes in MoCA scores presented significant improvements at discharge and three months follow-up tests. Conclusion: Awake brain mapping is a feasible and safe method for treating glioma invading the eloquent cortex, with the benefit of minimizing neurological deficits, increasing EOR, and extending survival time. The results of MoCA test indicated that brain mapping plays a critical role in preserving neurocognitive function during tumor resection.