Cost-effectiveness Analysis of Tumor Treating Fields Therapy Combined With Immune Checkpoint Inhibitor in Metastatic Non-small-cell Lung Cancer.

BACKGROUND: The LUNAR clinical trial revealed that incorporating Tumor Treating Fields (TTFields) therapy alongside immune checkpoint inhibitor (ICI) significantly prolonged the overall survival of patients with metastatic, platinum-resistant non-small-cell lung cancer (NSCLC). However, the cost of TTFields therapy is high and may further increase the financial burden for patients. Our research aims to evaluate the cost-effectiveness of TTFields therapy addition with ICI for metastatic NSCLC. METHODS: We constructed a Markov model to evaluate the healthcare costs associated with TTFields therapy combined with ICI for the treatment of advanced NSCLC. In this model, the clinical data utilized came from the LUNAR trial, while drug costs and health state utility values were extracted from public databases and relevant scholarly publications. The major outcomes incorporated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). RESULTS: Compared with ICI therapy alone, ICI combination with TTFields therapy resulted in 0.42 QALYs at the cost of $167,329, with an ICER of $398,402.38 per year. The calculated ICER surpassed the generally accepted US willingness-to-pay (WTP) threshold of 150,000 per QALY. One-way sensitivity analyses demonstrated that the utility of progression disease is the most influential factor, followed by the cost of TTFields therapy, the utility of progression-free survival, the cost of ICI, and the cost of adverse events in TTFields therapy combined with ICI. Only when the cost of TTFields therapy is reduced by approximately 80.48%, it would be cost-effective within the commonly accepted WTP threshold of $150,000/QALY. CONCLUSIONS: According to the US WTP, the combination of TTFields therapy with ICI does not currently represent a cost-effective strategy for metastatic NSCLC followed progression on platinum-resistant therapy. Considering its promising clinical outcomes for metastatic NSCLC, it is necessary to control the expenses of this therapeutic strategy in future applications.

Analysis of different surgical approaches to the treatment of thymoma.

BACKGROUND: Surgical approach in the treatment of thymoma is varied. This retrospective study aimed to evaluate the outcomes of different surgical approaches in the treatment of thymoma. METHODS: From January 2020 to December 2023, a total of 208 patients underwent thoracoscopic surgical treatment and were diagnosed with thymoma by postoperative pathological result in our institution. We collected and then analysed potential factors including general conditions, surgical approaches, preoperative clinical symptoms, surgical procedures, postoperative hospital stay, postoperative drainge, postoperative pain score, postoperative complications and postoperative follow-up. RESULTS: Of the 208 patients, 98 patients underwent surgery via subxiphoid approach (47.1%) and 110 patients via lateral intercostal approach (52.8%). The duration of the surgical procedure (P = 0.02), intraoperative blood loss (P = 0.045), total postoperative drainage (P = 0.021), postoperative drainage per day (P = 0.004) and Postoperative pain score (Day1 P = 0.010 and Day2 P = 0.002)showed a significant difference between these two groups. 31 patients (14.9%) received postoperative radiotherapy. One patient died due to postoperative radiotherapy. No recurrence occurred in one-year follow-up. CONCLUSIONS: The present study not only showed that subxiphoid approach was a safe and feasible technique for thymoma, with a potentially faster postoperative recovery and less postoperative pain.

Single-cell RNA sequencing and spatial transcriptomics of bladder Ewing sarcoma.

Bladder Ewing sarcoma/primitive neuroectodermal tumor (bladder ES/PNET) is a rare and highly malignant tumor associated with a poor prognosis, yet its underlying mechanisms remain poorly understood. Here, we employed a combination of single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and functional analyses to delve into the pathogenesis of bladder ES/PNET. The investigation revealed the presence of specialized types of epithelial cells (referred to as bladder ES-Epi) and mast cells (referred to as bladder ES-Mast) within bladder ES/PNET in comparison to urothelial carcinoma. Notably, TNFRSF12A exhibited significant upregulation in bladder ES/PNET. Furthermore, mast cells possessed the ability to activate epithelial cells through the TNFSF12-TNFRSF12A ligand-receptor signaling pattern. In addition, Enavatuzumab can significantly inhibit the migratory ability of the Ewing sarcoma cell line RD-ES. This groundbreaking study provides unprecedented mechanistic insights into the progression of bladder ES/PNET and introduces a potential therapeutic avenue for treating this challenging malignancy.

An Expanded Substrate Spectrum of Sulfide:Quinone Oxidoreductase Found in Pollutant-Degrading Bacteria.

Sulfide:quinone oxidoreductase (Sqr) catalyzes the initial procedure on sulfide transformation, alongside sulfide (H2S, S2-) oxidization coupled with coenzyme Q (CoQ) reducing and reactive sulfur species (RSS) production. Here, we assessed the reactivity of propanethiol (PT) as an alternative substrate for Sqr to maintain intracellular homeostasis in strain S-1 capable of degrading emerging sulfur-containing pollutants. We deleted a gene encoding Sqr, and serial transcriptional difference induced by RSS dynamics was therefore revealed. Next, the reaction properties of two Sqr homologs from strains JMP134 and S-1 were comparatively characterized, respectively. As a result, an additional role of Sqr in yielding RSS from PT was found in reaction mixture prepared by cell-free extracts or purified enzymes. Interestingly, the transformation velocity of PT by Sqr was slower than that of sulfides. From this scenario, it was a rate-determining step that PT as a nucleophilic compound can be added into Sqr cysteine to form disulfide bond and likely serve nonoptimal sulfur recipient. In addition, the role of persulfidation driven by RSS in combating oxidative and sulfur stresses required to be further clarified. Nevertheless, this promiscuity of Sqr-binding organosulfur compounds and its catalytic modulation underscored that expanded substrates might benefit sulfide homeostasis in thiol-degrading bacteria.

Divergence of Critical Fluctuations on Approaching Catastrophic Phase Inversion in Turbulent Emulsions.

Catastrophic phase inversion, the breakdown of a concentrated emulsion characterized by the most puzzling sudden feature, is crucial in numerous industrial applications. Here we combine well-controlled experiments and fully resolved numerical simulations to study the critical dynamics of catastrophic phase inversion in oil-water emulsions under turbulent flow as the phase-inversion volume fraction is approached. We reveal that the phase inversion is characterized by the critical power-law divergence of fluctuations in the global drag force. We determine the enhanced dynamical heterogeneity in the local droplet structures at approaching the phase inversion, and tightly connect it to the diverging drag fluctuations. Moreover, we show that near to the critical point the phase inversion is triggered as a stochastic process by large fluctuations at both large and small scales. Our findings pave the way to modeling the phase inversion process as an out-of-equilibrium critical-like phenomena.

Analysis of SLC genes alternative splicing identifies the SLC7A6 RI isoform as a therapeutic target for colorectal cancer.

Alternative splicing (AS), a crucial mechanism in post-transcriptional regulation, has been implicated in diverse cancer processes. Several splicing variants of solute carrier (SLC) transporters reportedly play pivotal roles in tumorigenesis and tumor development. However, an in-depth analysis of AS landscapes of SLCs in colon adenocarcinoma (COAD) is lacking. Herein, we analyzed data from The Cancer Genome Atlas and identified 1215 AS events across 243 SLC genes, including 109 differentially expressed AS (DEAS) events involving 62 SLC genes in COAD. Differentially spliced SLCs were enriched in biological processes, including transmembrane transporter activity, transporter activity, ferroptosis, and choline metabolism. In patients with COAD, tumor tissues exhibited higher expression of longer mitochondrial carrier SLC25A16 isoforms than adjacent normal tissues, consistent with bioinformatics analysis. Protein-coding sequences and transmembrane helices of survival-related DEAS were predicted, revealing that shifts in splicing sites altered the number and structure of their transmembrane proteins. We developed a prognostic risk model based on the screened 6-SLC-AS (SLC7A6_RI_37208 (SLC7A6-RI), SLC11A2_AP_21724, SLC2A8_ES_87631, SLC35B1_AA_42317, SLC39A11_AD_43204, and SLC7A8_AP_26712). Knockdown of the intronic region of SLC7A6-RI isoform enhanced colon cancer cell proliferation. In vivo, knockdown of the intronic region of SLC7A6-RI isoform enhanced tumor growth in colon cancer. Mechanistically, si-SLC7A6-RI isoform exerted oncogenic effects by activating the PI3K-Akt-mTOR signaling pathway and promoting cell proliferation, evidenced by increased expression of key regulators Phosphorylated Mammalian Target of Rapamycin (p-mTOR) and a cell proliferation marker Proliferating Cell Nuclear Antigen (PCNA) using western blotting. Our study elucidated SLC-AS in COAD, highlighting its potential as a prognostic and therapeutic target and emphasizing the suppressive influence of SLC7A6-RI in colon cancer progression.

Different multicellular trichome types coordinate herbivore mechanosensing and defense in tomato.

Herbivore-induced wounding can elicit a defense response in plants. However, whether plants possess a surveillance system capable of detecting herbivore threats and initiating preparatory defenses before wounding occurs remains unclear. In this study, we reveal that tomato (Solanum lycopersicum) trichomes can detect and respond to the mechanical stimuli generated by herbivores. Mechanical stimuli are preferentially perceived by long trichomes, and this mechanosensation is transduced via intra-trichome communication. This communication presumably involves calcium waves, and the transduced signals activate the jasmonic acid (JA) signaling pathway in short glandular trichomes, resulting in the upregulation of the Woolly (Wo)-SlMYC1 regulatory module for terpene biosynthesis. This induced defense mechanism provides plants with an early warning system against the threat of herbivore invasion. Our findings represent a perspective on the role of multicellular trichomes in plant defense and the underlying intra-trichome communication.

Worldwide research trends in Crohn's disease treatment over the past 2 decades: a bibliometric analysis.

Background: The treatment of Crohn's disease (CD) has received widespread attention in clinical practice, but there is currently a lack of quantitative evaluation of the literature published in this field. This study aimed to describe the development trends and research hotspots of CD treatment through bibliometric analysis. Methods: Publications related to CD treatment published from 2004 to 2023 were searched in the WoSCC. Microsoft Office Excel 2021 was used for the analysis and visualization of the annual number of publications. CiteSpace was used to visualize the collaboration networks of authors, institutions, and countries, as well as to construct a reference timeline visualization map and identify keywords with the strongest citation bursts. Results: The bibliometric analysis included 25,608 publications between 2004 and 2023. The most productive year was 2021. The United States of America (n = 7,891) and the University of California System (n = 939) are the country and institution with the most published papers, respectively. Among the 97,564 authors, Peyrin-Biroulet, Laurent (n = 424) published the most articles. The core journals were Inflammatory Bowel Diseases, Journal of Crohns and Colitis, Alimentary Pharmacology and Therapeutics, etc. The timeline view showed that "#5 JAK Inhibitor" was the most recent topic. The keywords that burst and persist from 2020 to 2023 include "ustekinumab" and "vedolizumab". Conclusion: An increasing number of researchers are dedicating their efforts to exploring the treatment of CD, with the United States making the largest contribution to this field. Currently, the research hotspots predominantly involve drug therapy including ustekinumab, vedolizumab, and JAK inhibitors. Our study provides valuable information for scholars studying CD treatment.

Gut bacteria of lepidopteran herbivores facilitate digestion of plant toxins.

Lepidopterans commonly feed on plant material, being the most significant insect herbivores in nature. Despite plant resistance to herbivory, such as producing toxic secondary metabolites, herbivores have developed mechanisms encoded in their genomes to tolerate or detoxify plant defensive compounds. Recent studies also highlight the role of gut microbiota in mediating detoxification in herbivores; however, convincing evidence supporting the significant contribution of gut symbionts is rare in Lepidoptera. Here, we show that the growth of various lepidopteran species was inhibited by a mulberry-derived secondary metabolite, 1-deoxynojirimycin (DNJ); as expected, the specialist silkworm Bombyx mori grew well, but interestingly, gut microbiota of early-instar silkworms was affected by the DNJ level, and several bacterial species responded positively to enriched DNJ. Among these, a bacterial strain isolated from the silkworm gut (Pseudomonas fulva ZJU1) can degrade and utilize DNJ as the sole energy source, and after inoculation into nonspecialists (e.g., beet armyworm Spodoptera exigua), P. fulva ZJU1 increased host resistance to DNJ and significantly promoted growth. We used genomic and transcriptomic analyses to identify genes potentially involved in DNJ degradation, and CRISPR-Cas9-mediated mutagenesis verified the function of ilvB, a key binding protein, in metabolizing DNJ. Furthermore, the ilvB deletion mutant, exhibiting normal bacterial growth, could no longer enhance nonspecialist performance, supporting a role in DNJ degradation in vivo. Therefore, our study demonstrated causality between the gut microbiome and detoxification of plant chemical defense in Lepidoptera, facilitating a mechanistic understanding of host-microbe relationships across this complex, abundant insect group.

Different Radiological Indices of Patellar Height Predict Patients' Diverse Outcomes Following Total Knee Arthroplasty.

Background: Total knee arthroplasty (TKA) is a common surgical procedure for patients with knee osteoarthritis. The patellar component plays a crucial role in knee biomechanics and can influence postoperative outcomes. This study aimed to investigate the relationship between radiological indices of patellar height and patient outcomes following TKA. Methods: A retrospective analysis was conducted on patients who underwent TKA for osteoarthritis. Radiographic measurements of patellar height, including the Insall-Salvati (IS) ratio, modified Blackburne-Peel (mBP) ratio, Caton-Deschamps ratio, and plateau-patellar angle (PPA), were obtained. Clinical outcomes were assessed using the Knee Society Score (KSS) and the Forgotten Joint Score-12 (FJS-12). Patient satisfaction and postoperative complications were also evaluated. Statistical analyses, including correlation analysis and multiple regression models, were performed to determine the association between radiological indices and patient outcomes. Results: The study included 330 cases that met the inclusion criteria. The analysis revealed significant correlations between different radiological indices of patellar height and patient outcomes. Lower postoperative PPA was correlated with worse KSS and range of motion scores. A decreased mBP ratio was associated with poorer FJS-12 responses and higher risks of dissatisfaction and patellar clunk or crepitus. Increased IS ratio was linked to a lower likelihood of incidental giving way of the knee. Advanced age was associated with reduced dissatisfaction and incidental giving way probabilities. Conclusions: The findings of this study demonstrate that radiological indices of patellar height can predict patient outcomes following TKA. Assessing patellar height using various radiographic measurements provides valuable information for surgical planning and prognostic evaluation. Understanding the impact of patellar height on clinical outcomes can aid in optimizing TKA procedures and improving patient satisfaction. These findings emphasize the importance of considering patellar height as a predictive factor in TKA and highlight its potential role in guiding postoperative management and rehabilitation strategies.

The humoral immune response of the lepidopteran model insect, silkworm Bombyx mori L., to microbial pathogens.

Insects are valuable models for studying innate immunity and its role in combating infections. The silkworm Bombyx mori L., a well-studied insect model, is susceptible to a range of pathogens, including bacteria, fungi, viruses, and microsporidia. Their susceptibility makes it a suitable model for investigating host-pathogen interactions and immune responses against infections and diseases. This review focuses on the humoral immune response and the production of antimicrobial peptides (AMPs), the phenoloxidase (PO) system, and other soluble factors that constitute the primary defense of silkworms against microbial pathogens. The innate immune system of silkworms relies on pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs), which then activate various immune pathways including Imd, Toll, JAK/STAT, and RNA interference (RNAi). Their activation triggers the secretion of AMPs, enzymatic defenses (lysozyme and PO), and the generation of reactive oxygen species (ROS). Collectively, these pathways work together to neutralize and eliminate pathogens, thereby contributing to the defense mechanism of silkworms. Understanding the innate immunity of silkworms can uncover conserved molecular pathways and key immune components shared between insects and vertebrates. Additionally, it can provide valuable insights for improving sericulture practices, developing strategies to control diseases affecting silk production, and providing a theoretical foundation for developing pest control measures.

Increased brain volume in the early phase of aneurysmal subarachnoid hemorrhage leads to delayed cerebral ischemia.

Objective: To investigate the correlation between the swelling rate of brain volume within the first 48 h after aneurysmal subarachnoid hemorrhage and the subsequent development of delayed cerebral ischemia. Methods: A retrospective analysis was conducted on patients with spontaneous aneurysmal subarachnoid hemorrhage admitted to the Neurosurgery Intensive Care Unit of the First Affiliated Hospital of Chongqing Medical University between January 2020 and January 2023. The clinical data, treatment outcomes, and imaging data were analyzed. Brain volume was evaluated using 3D-Slicer software at two time points post-hemorrhage: within the first 24 h and between 24 and 48 h. The swelling rate of brain volume was defined as the ratio of the absolute difference between two measurements to the smaller of values. Patients were categorized into two groups based on established diagnostic criteria of delayed cerebral ischemia. Univariate and multivariate logistic regression analyses were performed to identify factors influencing delayed cerebral ischemia. Results: A total of 140 patients were enrolled in this study. 46 patients experienced delayed cerebral ischemia after bleeding. The swelling rate of brain volume was larger in the DCI group (10.66 ± 8.45) compared to the non-DCI group (3.59 ± 2.62), which showed a statistically significant difference. Additionally, advanced age, smoking history, history of hypertension, loss of consciousness, poor Hunt-Hess grade, high mFisher score, brain volume within 24 h, and IVH were also statistically different between the two groups. Multivariate logistic regression analysis revealed that the swelling rate of brain volume was an independent risk factor for DCI with adjusting the advanced age, smoking history, history of hypertension, poor Hunt-Hess grade, high mFisher score, brain volume within 24 h, and IVH. Conclusion: Brain volume significantly increased in patients with aneurysmal subarachnoid hemorrhage during the early phase (within 48 h post-onset). The larger swelling rate of brain volume is an independent risk factor for the development of delayed cerebral ischemia, and it may hold significant predictive value for the incidence of delayed cerebral ischemia.

Development and validation of an explainable machine learning model for predicting multidimensional frailty in hospitalized patients with cirrhosis.

We sought to develop and validate a machine learning (ML) model for predicting multidimensional frailty based on clinical and laboratory data. Moreover, an explainable ML model utilizing SHapley Additive exPlanations (SHAP) was constructed. This study enrolled 622 patients hospitalized due to decompensating episodes at a tertiary hospital. The cohort data were randomly divided into training and test sets. External validation was carried out using 131 patients from other tertiary hospitals. The frail phenotype was defined according to a self-reported questionnaire (Frailty Index). The area under the receiver operating characteristics curve was adopted to compare the performance of five ML models. The importance of the features and interpretation of the ML models were determined using the SHAP method. The proportions of cirrhotic patients with nonfrail and frail phenotypes in combined training and test sets were 87.8% and 12.2%, respectively, while they were 88.5% and 11.5% in the external validation dataset. Five ML algorithms were used, and the random forest (RF) model exhibited substantially predictive performance. Regarding the external validation, the RF algorithm outperformed other ML models. Moreover, the SHAP method demonstrated that neutrophil-to-lymphocyte ratio, age, lymphocyte-to-monocyte ratio, ascites, and albumin served as the most important predictors for frailty. At the patient level, the SHAP force plot and decision plot exhibited a clinically meaningful explanation of the RF algorithm. We constructed an ML model (RF) providing accurate prediction of frail phenotype in decompensated cirrhosis. The explainability and generalizability may foster clinicians to understand contributors to this physiologically vulnerable situation and tailor interventions.

Progression of disease within 24 months (POD24) in multiple myeloma implicates poor prognosis and limitations of current prediction models for POD24.

Multiple myeloma (MM) is a common hematological malignancy, and its prognostic factors have been extensively studied. Progression of disease within 24 months (POD24) suggests a poor prognosis in many malignancies, but is rarely mentioned in MM. This study aimed to investigate the prognostic value of POD24 in MM and risk factors of POD24, and to evaluate the predictive value of existing MM prognostic models for POD24. The research retrospectively analyzed the clinical data of MM patients and found that the occurrence of POD24 is an independent prognostic factor affecting overall survival in MM, while non-transplantion and genetic abnormality are independent risk factors for the occurrence of POD24. The existing prognostic models are not effective in predicting POD24. Therefore, it's still necessary to explore a prognostic model that can predict POD24 more accurately.

Genome-based discovery of pachysiphine synthases in Tabernaemontana elegans.

Plant-specialized metabolism represents an inexhaustible source of active molecules, some of which have been used in human health for decades. Among these, monoterpene indole alkaloids (MIAs) include a wide range of valuable compounds with anticancer, antihypertensive, or neuroactive properties. This is particularly the case for the pachysiphine derivatives which show interesting antitumor and anti-Alzheimer activities but accumulate at very low levels in several Tabernaemontana species. Unfortunately, genome data in Tabernaemontanaceae are lacking and knowledge on the biogenesis of pachysiphine-related MIAs in planta remains scarce, limiting the prospects for the biotechnological supply of many pachysiphine-derived biopharmaceuticals. Here, we report a raw version of the toad tree (Tabernaemontana elegans) genome sequence. These new genomic resources led to the identification and characterization of a couple of genes encoding cytochrome P450 with pachysiphine synthase activity. Our phylogenomic and docking analyses highlight the different evolutionary processes that have been recruited to epoxidize the pachysiphine precursor tabersonine at a specific position and in a dedicated orientation, thus enriching our understanding of the diversification and speciation of the MIA metabolism in plants. These gene discoveries also allowed us to engineer the synthesis of MIAs in yeast through the combinatorial association of metabolic enzymes resulting in the tailor-made synthesis of non-natural MIAs. Overall, this work represents a step forward for the future supply of pachysiphine-derived drugs by microbial cell factories.

The impact of living environmental factors on cognitive function and mild cognitive impairment: evidence from the Chinese elderly population.

OBJECTIVES: Mild cognitive impairment represents a pivotal stage in the cognitive decline of older adults, with a considerable risk of advancing to dementia. Recognizing how living environmental factors affect cognition is crucial for crafting effective prevention and intervention strategies. This study seeks to elucidate the relationship between various living environmental factors and cognitive function, with a specific focus on mild cognitive impairment, within a Chinese elderly population. METHODS: This is a cross-section and longitudinal study. Utilizing data from CHARLS, our cross-sectional analysis included 4,401 participants, while the cohort study comprised 3,177 individuals. We assessed living environmental factors based on household fuel types, water sources, indoor temperatures, residential building types, and ambient PM2.5 levels. We employed multiple linear regression for cross-sectional analyses and Cox proportional hazards regression models for longitudinal assessments to determine the effects of living environments on cognitive function and MCI risk. Stratified analyses, interaction tests, and sensitivity analyses were conducted to further validate our findings. RESULTS: The findings revealed that, compared to those in high-risk environments, participants in low-risk settings exhibited higher cognitive scores (ß = 1.25, 95%CI: 0.85, 1.65), better mental status (ß = 0.70, 95%CI: 0.48, 0.92), and improved episodic memory (ß = 0.27, 95%CI: 0.13, 0.41). Over a 7-year follow-up, the use of low-risk living environments (HR = 0.67, 95%CI: 0.49, 0.91), including clean fuels (HR = 0.74, 95%CI: 0.57, 0.95) and tap water (HR = 0.84, 95%CI: 0.71, 1.00), demonstrated a protective effect against MCI development. This correlation remained significant regardless of age, gender, residence, education level, smoking, alcohol consumption, and depression. CONCLUSION: This research provides substantial evidence that living environmental factors significantly affect cognitive function and MCI risk in Chinese older adults. Enhancing living conditions may be a key strategy for promoting cognitive health and preventing MCI in this demographic. Further research is necessary to explore the long-term impacts and potential intervention strategies to optimize living environments for better cognitive outcomes in aging populations.

Bimolecular Passivation-Dipole Bridge for Highly Efficient Inverted Perovskite Solar Cells with Low Nonradiative Recombination Loss.

Constructing charge-selective heterointerface with minimized defect state and matched energy level alignment is essential to reduce nonradiative recombination for achieving high-performance perovskite solar cells (PSCs). Herein, a bimolecular passivation-dipole bridge comprised of sodium phenylmethanesulfonate (SPM) and 2-phenylethylammonium iodide (PEAI) is carefully developed to regulate perovskite heterointerface. SPM passivates defect states and upshifts Fermi level (EF) of perovskite surface, and subsequent PEAI further induces additional negative dipole and causes the surface EF of perovskite pinning to negative polaron transport state of electron transport layer PCBM, which significantly promotes electron extraction at the perovskite electron-selective contact. These advantages are confirmed by a remarkably improved efficiency from 21.74% for control to 25.12% for treated PSC with excellent stability. Moreover, corresponding nonradiative recombination loss impressively diminishes from 123 to 70 meV, and charge transport-induced fill factor loss is only 3.00%. This work provides a promising approach via passivation-energetic synergy for engineering perovskite heterointerface toward highly efficient and stable PSCs.

The SIRT5-Mediated Upregulation of C/EBPß Promotes White Adipose Tissue Browning by Enhancing UCP1 Signaling.

Sirtuin 5 (SIRT5) plays an important role in the maintenance of lipid metabolism and in white adipose tissue browning. In this study, we established a mouse model for diet-induced obesity and the browning of white fat; combined with gene expression intervention, transcriptome sequencing, and cell molecular biology methods, the regulation and molecular mechanisms of SIRT5 on fat deposition and beige fat formation were studied. The results showed that the loss of SIRT5 in obese mice exacerbated white adipose tissue deposition and metabolic inflexibility. Furthermore, the deletion of SIRT5 in a white-fat-browning mouse increased the succinylation of uncoupling protein 1 (UCP1), resulting in a loss of the beiging capacity of the subcutaneous white adipose tissue and impaired cold tolerance. Mechanistically, the inhibition of SIRT5 results in impaired CCAAT/enhancer binding protein beta (C/EBPß) expression in brown adipocytes, which in turn reduces the UCP1 transcriptional pathway. Thus, the transcription of UCP1 mediated by the SIRT5-C/EBPß axis is critical in regulating energy balance and obesity-related metabolism.

Ligand-controlled regiodivergent arylation of aryl(alkyl)alkynes and asymmetric synthesis of axially chiral 9-alkylidene-9,10-dihydroanthracenes.

Transition metal-catalyzed addition of organometallics to aryl(alkyl)alkynes has been well known to proceed with the regioselectivity in forming a carbon-carbon bond at the alkyl-substituted carbon (ß-addition). Herein, the reverse regiochemistry with high selectivity in giving 1,1-diarylalkenes (α-addition) was realized in the reaction of arylboronic acids with aryl(alkyl)alkynes by use of a rhodium catalyst coordinated with a chiral diene ligand, whereas the arylation of the same alkynes proceeded with the usual regioselectivity (ß-addition) in the presence of a rhodium/DM-BINAP catalyst. The regioselectivity can be switched by the choice of ligands on the rhodium catalysts. This reverse regioselectivity also enabled the catalytic asymmetric synthesis of phoenix-like axially chiral alkylidene dihydroanthracenes with high enantioselectivity through an α-addition/1,4-migration/cyclization sequence.

Selective Oxidation of p-Cymene over Mesoporous LaCoO3 by Introducing Oxygen Vacancies.

The liquid-phase catalytic oxidation of p-cymene to 4-methylacetophenone is an industrially significant reaction. However, the targeted oxidation of a specific C-H bond of p-cymene is extremely difficult due to there being many branched chains in p-cymene. In here, we designed a simple method to synthesize mesoporous LaCoO3 catalysts with rich oxygen vacancy (Oov) sites. The as-prepared mesoporous LaCoO3 after 550 °C calcination (mLaCoO3) exhibits remarkable catalytic activity for solvent-free oxidation of the p-cymene reaction, with a selectivity of over 80.1% selectivity for 4-methylacetophenone and a conversion of 50.2% for p-cymene (120 °C, 3 MPa). Besides, recycling studies have demonstrated that the mLaCoO3 catalysts can be reused ten times in the aerobic oxidation of the p-cymene reaction without significant catalytic activity reduce. The experimental and characterization results indicated that the mesoporous structure of the catalyst is conducive to the generation of surface Oov, which can properly facilitate ion spread during the catalytic process and afford enough O2 for intermediate species, thus is beneficial for the generation of 4-methylacetophenone. This work demonstrates that the selectivity oxide p-cymene with an O2 employing mLaCoO3 catalyst is highly promising for chemical industrial applications.