Clinical Characteristics, Genetic Analysis, and Literature Review of Cornelia de Lange Syndrome Type 4 Associated With a RAD21 Variant.

BACKGROUND: Cornelia de Lange syndrome (CdLS) is an uncommon congenital developmental disorder distinguished by intellectual disorder and distinctive facial characteristics, with a minority of cases attributed to RAD21 variants. METHODS: A patient was admitted to the endocrinology department at Peking Union Medical College Hospital, where 2 mL of peripheral venous blood was collected from the patient and his parents. DNA was extracted for whole-exome sequencing (WES) analysis, and the genetic variation of the parents was confirmed through Sanger sequencing. RESULTS: A 13.3-year-old male patient with a height of 136.5 cm (-3.5 SDS) and a weight of 28.4 kg (-3.1 SDS) was found to have typical craniofacial features. WES revealed a pathogenic variant c.1143G>A (p.Trp381*) in the RAD21 gene. He was diagnosed with CdLS type 4 (OMIM #614701). We reviewed 36 patients with CdLS related to RAD21 gene variants reported worldwide from May 2012 to March 2024. Patient's variant status, clinical characteristics, and rhGH treatment response were summarized. Frameshift variants constituted the predominant variant type, representing 36% (13/36) of cases. Clinical features included verbal developmental delay and intellectual disorder observed in 94% of patients. CONCLUSION: This study reported the third case of CdLS type 4 in China caused by a RAD21 gene variant, enriching the genetic mutational spectrum.

Manganese Doped-Nitrogenated Carbon as an Efficient Catalyst for Acidic Electrocatalytic Reduction of CO2.

Renewable electricity-driven CO2 electroreduction to value-added chemicals is a feasible approach to alleviate both environmental and energy issues. However, CO2 reduction reaction (CO2RR) systems in alkaline electrolytes are constrained by intrinsic limitations such as salt accumulation that impede further industrialization. Herein, an atomically dispersed Mn doped-nitrogen carbon (AD MnNC) catalyst is developed to electrochemically reduce CO2 to CO in both neutral and acidic media. Benefiting from well-dispersed MnNx sites, the maximum CO Faradaic efficiency (FECO) reaches ≈100% at -0.73 V versus reversible hydrogen electrode (RHE) with CO current density (JCO) of 20.4 mA cm-2 in neutral 0.5 m KHCO3. Due to diminished *H adsorption, AD MnNC achieves a FECO of 85.3% at pH 2.0, effectively suppressing the hydrogen evolution reaction (HER) in an acidic electrolyte. The mechanistic study reveals that AD MnNC accelerates the production of *COOH intermediates through a proton-coupled electron transfer (PCET) pathway and thus promotes CO formation.

Complete genome sequence analysis of Pestalotiopsis microspora, a fungal pathogen causing kiwifruit postharvest rots.

BACKGROUND: The postharvest rot of kiwifruit is one of the most devastating diseases affecting kiwifruit quality worldwide. However, the genomic basis and pathogenicity mechanisms of kiwifruit rot pathogens are lacking. Here we report the first whole genome sequence of Pestalotiopsis microspora, one of the main pathogens causing postharvest kiwifruit rot in China. The genome of strain KFRD-2 was sequenced, de novo assembled, and analyzed. RESULTS: The genome of KFRD-2 was estimated to be approximately 50.31 Mb in size, with an overall GC content of 50.25%. Among 14,711 predicted genes, 14,423 (98.04%) exhibited significant matches to genes in the NCBI nr database. A phylogenetic analysis of 26 known pathogenic fungi, including P. microspora KFRD-2, based on conserved orthologous genes, revealed that KFRD-2's closest evolutionary relationships were to Neopestalotiopsis spp. Among KFRD-2's coding genes, 870 putative CAZy genes spanned six classes of CAZys, which play roles in degrading plant cell walls. Out of the 25 other plant pathogenic fungi, P. microspora possessed a greater number of CAZy genes than 22 and was especially enriched in GH and AA genes. A total of 845 transcription factors and 86 secondary metabolism gene clusters were predicted, representing various types. Furthermore, 28 effectors and 109 virulence-enhanced factors were identified using the PHI (pathogen host-interacting) database. CONCLUSION: This complete genome sequence analysis of the kiwifruit postharvest rot pathogen P. microspora enriches our understanding its disease pathogenesis and virulence. This study establishes a theoretical foundation for future investigations into the pathogenic mechanisms of P. microspora and the development of enhanced strategies for the efficient management of kiwifruit postharvest rots.

Ligand-to-Metal Charge Transfer (LMCT) Catalysis: Harnessing Simple Cerium Catalysts for Selective Functionalization of Inert C-H and C-C Bonds.

ConspectusChemists have long pursued harnessing light energy and photoexcitation processes for synthetic transformations. Ligand-to-metal charge transfer (LMCT) in high-valent metal complexes often triggers bond homolysis, generating oxidized ligand-centered radicals and reduced metal centers. While photoinduced oxidative activations can be enabled, this process, typically seen as photochemical decomposition, remains underexplored in catalytic applications. To mitigate decomposition during LMCT excitation, we developed a catalytic cycle integrating in situ coordination, LMCT, and ligand homolysis to activate ligated alcohols transiently into alkoxy radicals. This catalytic approach leverages Ce(IV) LMCT excitation and highly reactive alkoxy radical intermediates for selective functionalizations of C(sp3)-H and C(sp3)-C(sp3) bonds under mild conditions. In this Account, we discuss these advancements, highlighting the practical utility of cost-effective cerium salts as catalysts and their potential to develop innovative transformations, addressing long-standing synthetic challenges.Selective functionalization of chemically inert C(sp3)-H bonds has long posed a significant challenge. We first detail our research using LMCT-enabled alkoxy radical-mediated hydrogen atom transfer (HAT) processes for selective C(sp3)-H functionalizations. Using readily available CeCl3, we established a general protocol for employing free alcohols in the Barton reaction. By integrating LMCT and HAT catalysis, we introduced a selective photocatalytic strategy for functionalizing feedstock alkanes, converting gaseous hydrocarbons into valuable products. Employing simple cerium salts like Ce(OTf)3 and CeCl3, we achieved selective C-H amination of methane and ethane at ambient temperature, achieving turnover numbers of 2900 and 9700, respectively. This catalytic manifold has been further exploited to address the site-selectivity challenge in the C-H functionalization of linear alkanes. The use of methanol as a cocatalyst enabled preferential functionalization of the most electron-rich sites, achieving a high intrinsic selectivity over 12:1 of secondary vs primary sites in pentane and hexane.Next, we discuss the catalytic utilization of alkoxy-radical-mediated ß-scission, a frequently encountered side reaction in HAT transformations, for selective cleavage and functionalization of C-C bonds. The versatility of the LMCT catalytic platform facilitates the generation of alkoxy radicals from various free alcohols. In our initial demonstration of LMCT-enabled C(sp3)-C(sp3) bond activation, we developed a cerium-catalyzed ring-opening and amination of cycloalkanols, providing an effective protocol for cleaving unstrained C-C bonds. This strategy has been successfully applied to various radical cross-coupling processes, leading to innovative transformations such as ring expansions of cycloalkanols, dehydroxymethylative alkylation, amination, alkenylation, and ring expansions of cyclic ketones. These results highlight the synthetic potential of employing LMCT-mediated ß-scission and ubiquitous C-C bonds as unconventional functional handles for generating molecular complexity.Lastly, we delve into our mechanistic investigations. Beyond the catalytic application of Ce(IV) LMCT in various transformations, we have undertaken comprehensive mechanistic studies. These investigations encompass characterization of Ce(IV) alkoxide complexes to elucidate their structures, evaluation of their photoactivity and selectivity in radical generation, and elucidation of kinetic pathways associated with transient LMCT excited states. Our research has revealed ultrafast bond homolysis, back electron transfer, and the selectivity of heteroleptic complexes in homolysis, providing crucial insights for advancing LMCT catalysis.

Evaluating the toxicity effects of thiamethoxam and its main metabolite clothianidin to earthworms (Eisenia fetida) from the perspective of endogenous metabolites.

The widespread application of neonicotinoid insecticides (NNIs) has attracted widespread attention to their potential ecotoxicological effects. In this study, we systematically evaluated the toxic effects of thiamethoxam (TMX) and its metabolite clothianidin (CLO) on earthworms (Eisenia fetida). Specifically, the antioxidant system responses and endogenous metabolite metabolism responses in earthworms were analyzed in the temporal dimension after 7, 14, 21 and 28 days of exposure to TMX and CLO. The results found that TMX and CLO could inhibit the growth phenotype of earthworms and cause significant changes in antioxidant system related indicators. More importantly, we found that TMX and CLO could cause significant changes in the metabolic profiles of earthworms through NMR-based metabolomics. From the changes in endogenous metabolites, the toxicity effects of TMX on earthworms gradually increases with prolonged exposure time. Differently, the toxicity effects of CLO on earthworms is significantly higher than that of TMX in the early stages of exposure. Meanwhile, these impacts will not weaken with prolonged exposure time. Furthermore, the results of KEGG enrichment pathway analysis indicated that TMX and CLO could significantly interfere with energy homeostasis, redox homeostasis, osmotic regulation, amino acid metabolism and protein synthesis in earthworms. These findings further deepen our understanding of the ecotoxicological effects of NNIs on soil organism.

Genetic diseases are not necessarily inherited: suggestion on its Chinese translation.

From Mendel's discovery of the basic laws of genetics in 1865 to the widespread application of genomics in medicine today, medical genetics has made enormous progress, and the concept of genetic diseases has also been evolved. In 1972, the World Health Organization (WHO) expert group began to use "Genetic Disease" to define hereditary diseases, while early Chinese genetics textbooks used "inferior inheritance", and later introduced terms such as "Genetic Disease" and "Inherited Disease". In the early days, it was generally believed that genetic diseases were inherited from ancestors. However, research in recent years has found that genetic diseases are not necessarily inherited, and some diseases are actually caused by de novo mutations in the offspring. Although the occurrence of this type of genetic disease is related to genetic factors, it is not inherited from ancestors. If we still use "Inherited Disease" or "Hereditary Disease" to describe it, it is not accurate enough. In order to further standardize the translation and use of the concept of "Genetic Disease", this article briefly reviews its development process in both English and Chinese literature, discusses the difference between different Chinese translations, and provides guidance and suggestions for scientifically and accurately describing genetic diseases in Chinese, with a view to promote efficient exchange and cooperation in the field of medical genetics.

Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance.

BACKGROUND: The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or 'endozepine') increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer. METHODS: We measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing. RESULTS: Circulating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers. CONCLUSION: These findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance.

Postprandial metabolomics analysis reveals disordered serotonin metabolism in post-bariatric hypoglycemia.

BACKGROUND: Bariatric surgery is a potent therapeutic approach for obesity and type 2 diabetes but can be complicated by post-bariatric hypoglycemia (PBH). PBH typically occurs 1 to 3 hours after meals, in association with exaggerated postprandial levels of incretins and insulin. METHODS: To identify mediators of disordered metabolism in PBH, we analyzed plasma metabolome in fasting state and 30 and 120 minutes after mixed meal in 3 groups: PBH (n = 13), asymptomatic post-RYGB (n = 10), and non-surgical controls (n = 8). RESULTS: In the fasting state, multiple tricarboxylic acid cycle intermediates and the ketone beta-hydroxybutyrate were increased by 30% to 80% in PBH vs. asymptomatic. Conversely, multiple amino acids (BCAA, tryptophan) and polyunsaturated lipids were reduced by 20% to 50% in PBH versus asymptomatic. Tryptophan-related metabolites, including kynurenate, xanthurenate, and serotonin, were reduced by 2- to 10-fold in PBH in fasting state. Postprandially, plasma serotonin was uniquely increased by 1.9-fold in PBH versus asymptomatic post-RYGB. In mice, serotonin administration lowered glucose and increased plasma insulin and GLP-1. Moreover, serotonin-induced hypoglycemia in mice was blocked by the nonspecific serotonin receptor antagonist cyproheptadine and the specific serotonin receptor 2 antagonist ketanserin. CONCLUSION: Together these data suggest that increased postprandial serotonin may contribute to the pathophysiology of PBH and provide a potential therapeutic target. FUNDING: NIH grant R01 DK121995, NIH grant P30 DK036836 (Diabetes Research Center grant, Joslin Diabetes Center), and Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP grant 2018/22111-2.

Matrisome proteomics reveals novel mediators of muscle remodeling with aerobic exercise training.

Skeletal muscle has a unique ability to remodel in response to stimuli such as contraction and aerobic exercise training. Phenotypic changes in muscle that occur with training such as a switch to a more oxidative fiber type, and increased capillary density contribute to the well-known health benefits of aerobic exercise. The muscle matrisome likely plays an important role in muscle remodeling with exercise. However, due to technical limitations in studying muscle ECM proteins, which are highly insoluble, little is known about the muscle matrisome and how it contributes to muscle remodeling. Here, we utilized two-fraction methodology to extract muscle proteins, combined with multiplexed tandem mass tag proteomic technology to identify 161 unique ECM proteins in mouse skeletal muscle. In addition, we demonstrate that aerobic exercise training induces remodeling of a significant proportion of the muscle matrisome. We performed follow-up experiments to validate exercise-regulated ECM targets in a separate cohort of mice using Western blotting and immunofluorescence imaging. Our data demonstrate that changes in several key ECM targets are strongly associated with muscle remodeling processes such as increased capillary density in mice. We also identify LOXL1 as a novel muscle ECM target associated with aerobic capacity in humans. In addition, publically available data and databases were used for in silico modeling to determine the likely cellular sources of exercise-induced ECM remodeling targets and identify ECM interaction networks. This work greatly enhances our understanding of ECM content and function in skeletal muscle and demonstrates an important role for ECM remodeling in the adaptive response to exercise. The raw MS data have been deposited to the ProteomeXchange with identifier PXD053003.

Engineered cyanobacteria-Fe3O4 hybrid system as oxygen generator and photosensitizer production factory for synergistic cancer PDT-immunotherapy.

The combination of photodynamic therapy (PDT)-immunotherapy has brought much hope for cancer patients. However, the hypoxia tumor microenvironment (TME) can regulate tumor angiogenesis and inhibit immune response, thus limiting the therapeutic effects. In this paper, engineered cyanobacteria-M2-like tumor-associated macrophages (TAMs) targeting peptide modified Fe3O4 nanoparticles hybrid system (ECyano@Fe3O4-M2pep) was constructed for alleviating hypoxia and relieving immune suppression to achieve synergistic cancer PDT-immunotherapy. With the irradiation of red laser, oxygen was produced by the photosynthesis of ECyano to alleviate the hypoxia TME. Then, ECyano could secret 5-aminolevulinic acid (5-ALA) under the induction of theophylline for controllable PDT. In the process of PDT, the disulfide bond between ECyano and Fe3O4-M2pep was broken in response to reactive oxygen species (ROS), and then Fe3O4-M2pep was released to target M2-like TAMs, corresponding by the polarization of M2-like TAMs to M1-like TAMs for the killing of tumor cells. Compared with other groups, ECyano@Fe3O4-M2pep + theophylline + laser (ECyano@Fe3O4-M2pep + T + L) group displayed the lowest tumor volume (159.3 mm3) and the highest M1/M2 ratio (1.25- fold). We believe that this hybrid system will offer a promising way for the biomedical application of bacterial therapy.

Spermidine is essential for fasting-mediated autophagy and longevity.

Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders. Here, we asked whether the cellular and physiological consequences of caloric restriction and fasting depend on polyamine metabolism. We report that spermidine levels increased upon distinct regimens of fasting or caloric restriction in yeast, flies, mice and human volunteers. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, nematodes and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan- and healthspan-extending effects, as well as the cardioprotective and anti-arthritic consequences of fasting. Mechanistically, spermidine mediated these effects via autophagy induction and hypusination of the translation regulator eIF5A. In summary, the polyamine-hypusination axis emerges as a phylogenetically conserved metabolic control hub for fasting-mediated autophagy enhancement and longevity.

Acyl-CoA binding protein for the experimental treatment of anorexia.

Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.

Oral Levodopa Stimulates Copeptin Secretion in Children and Adolescents with Intact Posterior Pituitary Function.

BACKGROUND: Copeptin stimulation tests can be used in the differential diagnosis of polyuria polydipsia syndrome. Current stimulation methods rely on intravenous or subcutaneous administration. Oral stimulus can further simplify the diagnostic approach. The levodopa stimulation test is widely used in the evaluation of growth hormone deficiency (GHD), and the dopamine pathway was reported to be associated with arginine vasopressin secretion. The study aimed to investigate the effect of oral levodopa on copeptin secretion. METHODS: The study was a prospective observational single-center cohort study. Patients < 18 years old with short stature and no symptoms of polyuria or polydipsia undergoing levodopa stimulation test for suspected GHD were recruited from May 2023 to Nov 2023. Copeptin and growth hormone (GH) were measured at 0, 30, 60, 90, and 120min in the levodopa test. The insulin tolerance test with copeptin and GH measured at the same time points was conducted in part of patients. RESULTS: Forty-four participants were included in the final analysis. In the levodopa stimulation test, the median (interquartile range, IQR) copeptin concentration increased from 5.20 (3.51, 8.25) pmol/L to maximum 19.36 (8.97, 108.08) pmol/L (P < 0.001), 3.94 (1.41, 13.88) times of the baseline (P < 0.001). Compared with insulin tolerance test, peak copeptin in the levodopa test was significantly higher (34.61 (13.67, 98.96) vs 8.88 (7.14, 15.42) pmol/L, P = 0.009). Higher copeptin was associated with larger dose of levodopa. CONCLUSIONS: Oral levodopa could be used to stimulate copeptin.

Reactive oxygen species sensitive nanomicelles promote the antifungal activity of ketoconazole against Candida albicans in vulvovaginal candidiasis.

Excessive local accumulation of reactive oxygen species (ROS) in vulvovaginal candidiasis (VVC) leads to oxidative stress and aggravates inflammation. This study aimed to optimize and synthesize four ROS-sensitive polyethylene glycol (PEG)-boride polymers (PB, PCB, BPB, and BCPCB). A nanomicelle (BCPCB-K) was constructed using BCPCB-encapsulated ketoconazole (KTZ). Finally, the depolymerization principle and ROS-sensitive drug release of BCPCB-K as well as its anti-Candida albicans (CA) and therapeutic effects on mice with VVC were explored through in vitro and in vivo experiments. BCPCB-K exhibited low toxicity to mammalian cells in vitro and good biocompatibility in vivo. It also improved the dispersion and solubility of the hydrophobic drug KTZ. Furthermore, BCPCB-K simultaneously scavenged ROS and released the drug, thus facilitating the antifungal and VVC-treating effects of KTZ. Overall, the findings of this study broadened the application of ROS-sensitive materials in the drug-loading and antifungal fields and provided a strategy for VVC treatment.

Electrolyte-Assisted Structure Reconstruction Optimization of Sn-Zn Hybrid Oxide Boosts the Electrochemical CO2-to-HCOO- Conversion.

Electrolyte plays crucial roles in electrochemical CO2 reduction reaction (e-CO2RR), yet how it affects the e-CO2RR performance still being unclarified. In this work, it is reported that Sn-Zn hybrid oxide enables excellent CO2-to-HCOO- conversion in KHCO3 with a HCOO- Faraday efficiency ≈89%, a yield rate ≈0.58 mmol cm-2 h-1 and a stability up to ≈60 h at -0.93 V, which are higher than those in NaHCO3 and K2SO4. Systematical characterizations unveil that the surface reconstruction on Sn-Zn greatly depends on the electrolyte using: the Sn-SnO2/ZnO, the ZnO encapsulated Sn-SnO2/ZnO and the Sn-SnO2/Zn-ZnO are reconstructed on the surface by KHCO3, NaHCO3 and K2SO4, respectively. The improved CO2-to-HCOO- performance in KHCO3 is highly attributed to the reconstructed Sn-SnO2/ZnO, which can enhance the charge transportation, promote the CO2 adsorption and optimize the adsorption configuration, accumulate the protons by enhancing water adsorption/cleavage and limit the hydrogen evolution. The findings may provide insightful understanding on the relationship between electrolyte and surface reconstruction in e-CO2RR and guide the design of novel electrocatalyst for effective CO2 reduction.

Coupled Ni─Co Dual-Atom Catalyst for Guiding Sulfur and Lithium Evolutions in Lithium-Sulfur Batteries.

The kinetically retarded sulfur evolution reactions and notorious lithium dendrites as the major obstacles hamper the practical implementation of lithium-sulfur batteries (LSBs). Dual metal atom catalysts as a new model are expected to show higher activity by their rational coupling. Herein, the dual-atom catalyst with coupled Ni─Co atom pairs (Ni/Co-DAC) is designed successfully by programmed approaches. The Ni─Co atom pairs alter the local electron structure and optimize the coordination configuration of Ni/Co-DAC, leading to the coupling effect for promoting the interconversion of sulfur and guiding lithium plating/striping. The LSB delivers a remarkable capacity of 818 mA h g-1 at 3.0 C and a low degeneration rate of 0.053% per cycle over 500 cycles. Moreover, the LSB with a high sulfur mass loading of 6.1 mg cm-2 and lean electrolyte dosage of 6.0 µL mgS -1 shows a remarkable areal capacity of 5.7 mA h cm-2.

Bithieno[3,4-c]pyrrole-4,6-dione-Based Wide-Bandgap Donor Polymers for Efficient Polymer Solar Cells.

The polymer solar cells (PSCs) have garnered substantial interest owing to their lightweight, cost-effectiveness, and flexibility, making them ideal for large-scale roll-to-roll manufacturing. In this study, two wide-bandgap (WBG) donor polymers, PFBiTPD and PClBiTPD, utilizing bithieno[3,4-c]pyrrole-4,6-dione (BiTPD) as the electron-accepting unit and fluorinated/chlorinated benzo[1,2-b:4,5-b']dithiophene (BDT) as the electron-donating moiety are designed and synthesized. The polymers demonstrated large optical bandgaps (exceeding 1.80 eV) and are blended with ITIC-4F to form the active layers in PSCs. The PFBiTPD-based devices showed a well-dispersed fibrillar network, facilitating efficient charge generation and transport. Thus, these devices attained a power conversion efficiency (PCE) of 8.60%, featuring a fill factor (FF) of 62.89%, an open-circuit voltage (Voc) of 0.88 V and a short-circuit current density (Jsc) of 15.54 mA cm-2. In contrast, PClBiTPD-based devices displayed lower performance due to less favorable morphology. The study underscores the importance of polymer design and morphology control in optimizing the photovoltaic performance of PSCs.

Mechanism research of non-coding RNA in immune checkpoint inhibitors therapy.

Immune checkpoint inhibitor (ICI) therapies for tumors of different systems have attained significant achievements and have changed the current situation of tumor treatment due to their therapeutic characteristics of high specificity and low side effects. The immune checkpoint Programmed death 1/Programmed cell death-Ligand 1 (PD-1/PD-L1) axis exerts a vital role in the immune escape of tumor cells. As a result, it has become a key target for tumor immunotherapy. Therefore, to perfect research into potential regulatory factors for the PD-1/PD-L1 axis, in order to understand and illustrate tumor ICI therapy mechanisms, is a significant goal. Moreover, ncRNA has been verified to regulate the PD-1/PD-L1 axis in the tumor immune microenvironment to regulate tumor genesis and development. ncRNAs can improve or decrease the efficacy of ICI therapy by modulating PD-L1 expression. This review aimed to investigate the mechanisms of action of ncRNA in regulating the PD-1/PD-L1 axis in ICI therapy, to provide more efficient immunotherapy for tumors of different systems.

APOE ε4-associated downregulation of the IL-7/IL-7R pathway in effector memory T cells: Implications for Alzheimer's disease.

INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.