The role of JMJD2A in immune evasion and malignant behavior of esophageal squamous cell carcinoma.

OBJECTIVE: This study aimed to investigate the role of JMJD2A in radiotherapy tolerance of esophageal squamous cell carcinoma (ESCC). METHODS: The levels of H3K9me3 modification were analyzed in anti-PD-1 therapy non-responder or responder patients, and the expression differences of H3K9me3-related modifying enzymes were assessed in TCGA-ESCC and ICGC cohorts. Subsequently, JMJD2A was knocked down in ESCC cells using CRISPR-Cas9 or lentivirus-mediated shRNA, and changes in malignant behavior of ESCC cells were observed. RNA-seq, ATAC-seq, and ChIP-seq analyses were then conducted to investigate the genes and downstream signaling pathways regulated by JMJD2A, and functional validation experiments were performed to analyze the role of downstream regulated genes and pathways in ESCC malignant behavior and immune evasion. RESULTS: JMJD2A was significantly overexpressed in ESCC and anti-PD-1 therapy non-responders. Knockdown or deletion of JMJD2A significantly promoted the malignant behavior and immune evasion of ESCC. JMJD2A facilitated the structural changes in chromatin and promoted the binding of SMARCA4 to super-enhancers, thereby inducing the expression of GPX4. This resulted in the inhibition of radiation-induced DNA damage and cell ferroptosis, ultimately promoting the malignant behavior and immune evasion of ESCC cells. CONCLUSION: JMJD2A plays an indispensable role in the malignant behavior and immune evasion of ESCC. It regulates the binding of SMARCA4 to super-enhancers and affects the chromatin's epigenetic landscape, thereby promoting the expression of GPX4 and attenuating iron-mediated cell death caused by radiotherapy. Consequently, it triggers the malignant behavior and immune evasion of ESCC cells.

Lactate-induced activation of tumor-associated fibroblasts and IL-8-mediated macrophage recruitment promote lung cancer progression.

Alterations in the tumor microenvironment are closely associated with the metabolic phenotype of tumor cells. Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor growth and metastasis. Existing studies have suggested that lactate produced by tumor cells can activate CAFs, yet the precise underlying mechanisms remain largely unexplored. In this study, we initially identified that lactate derived from lung cancer cells can promote nuclear translocation of NUSAP1, subsequently leading to the recruitment of the transcriptional complex JUNB-FRA1-FRA2 near the DESMIN promoter and facilitating DESMIN transcriptional activation, thereby promoting CAFs' activation. Moreover, DESMIN-positive CAFs, in turn, secrete IL-8, which recruits TAMs or promotes M2 polarization of macrophages, further contributing to the alterations in the tumor microenvironment and facilitating lung cancer progression. Furthermore, we observed that the use of IL-8 receptor antagonists, SB225002, or Navarixin, significantly reduced TAM infiltration and enhanced the therapeutic efficacy of anti-PD-1 or anti-PD-L1 treatment. This finding indicates that inhibiting IL-8R activity can attenuate the impact of CAFs on the tumor microenvironment, thus restraining the progression of lung cancer.

From metabolism to malignancy: the multifaceted role of PGC1α in cancer.

PGC1α, a central player in mitochondrial biology, holds a complex role in the metabolic shifts seen in cancer cells. While its dysregulation is common across major cancers, its impact varies. In some cases, downregulation promotes aerobic glycolysis and progression, whereas in others, overexpression escalates respiration and aggression. PGC1α's interactions with distinct signaling pathways and transcription factors further diversify its roles, often in a tissue-specific manner. Understanding these multifaceted functions could unlock innovative therapeutic strategies. However, challenges exist in managing the metabolic adaptability of cancer cells and refining PGC1α-targeted approaches. This review aims to collate and present the current knowledge on the expression patterns, regulators, binding partners, and roles of PGC1α in diverse cancers. We examined PGC1α's tissue-specific functions and elucidated its dual nature as both a potential tumor suppressor and an oncogenic collaborator. In cancers where PGC1α is tumor-suppressive, reinstating its levels could halt cell proliferation and invasion, and make the cells more receptive to chemotherapy. In cancers where the opposite is true, halting PGC1α's upregulation can be beneficial as it promotes oxidative phosphorylation, allows cancer cells to adapt to stress, and promotes a more aggressive cancer phenotype. Thus, to target PGC1α effectively, understanding its nuanced role in each cancer subtype is indispensable. This can pave the way for significant strides in the field of oncology.

Engineering of Halide Methyltransferase BxHMT through Dynamic Cross-Correlation Network Analysis.

Halide methyltransferases (HMTs) provide an effective way to regenerate S-adenosyl methionine (SAM) from S-adenosyl homocysteine and reactive electrophiles, such as methyl iodide (MeI) and methyl toluene sulfonate (MeOTs). As compared with MeI, the cost-effective unnatural substrate MeOTs can be accessed directly from cheap and abundant alcohols, but shows only limited reactivity in SAM production. In this study, we developed a dynamic cross-correlation network analysis (DCCNA) strategy for quickly identifying hot spots influencing the catalytic efficiency of the enzyme, and applied it to the evolution of HMT from Paraburkholderia xenovorans. Finally, the optimal mutant, M4 (V55T/C125S/L127T/L129P), exhibited remarkable improvement, with a specific activity of 4.08 U/mg towards MeOTs, representing an 82-fold increase as compared to the wild-type (WT) enzyme. Notably, M4 also demonstrated a positive impact on the catalytic ability with other methyl donors. The structural mechanism behind the enhanced enzyme activity was uncovered by molecular dynamics simulations. Our work not only contributes a promising biocatalyst for the regeneration of SAM, but also offers a strategy for efficient enzyme engineering.

Exploring the causal relationship between antihypertensive drugs and glioblastoma by combining drug target Mendelian randomization study, eQTL colocalization, and single-cell RNA sequencing.

Recent reports indicate a potential oncogenic role of antihypertensive drugs in common cancers. However, it remains uncertain whether this phenomenon influences the risk of glioblastoma multiforme (GBM). This study aimed to assess the potential causal effects of blood pressure (BP) and antihypertensive drugs on GBM. Genome-wide association study (GWAS) summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), and GBM in Europeans were downloaded. To represent the effects of antihypertensive drugs, we utilized single nucleotide polymorphisms (SNPs) associated with SBP/DBP adjacent to the coding regions of different antihypertensive drugs as instrumental variables to model five antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, ß-receptor blockers (BBs), and thiazide diuretics. Positive control studies were performed using GWAS data in chronic heart failure. The primary method for causality estimation was the inverse-variance-weighted method. Mendelian randomization analysis showed that BBs with the ß1-adrenergic receptor (ADRB1) as a therapeutic target could significantly reduce the risk of GBM by mediating DBP (OR = 0.431, 95% CI: 0.267-0.697, p < .001) and that they could also significantly reduce the risk of GBM by mediating SBP (OR = 0.595, 95% CI: 0.422-0.837, p = .003). Sensitivity analysis and colocalization analysis reinforced the robustness of these findings. Finally, the low expression of the ADRB1 gene in malignant gliomas was found by GBM data from TCGA and single-cell RNA sequencing, which most likely contributed to the poor prognosis of GBM patients. In summary, our study provides preliminary evidence of some causal relationship between ADRB1-targeted BBs and glioblastoma development. However, more studies are needed to validate these findings and further reveal the complex relationship between BP and GBM.

Erratum: Involvement of miR-619-5p in resistance to cisplatin by regulating ATXN3 in oral squamous cell carcinoma: Erratum.

[This corrects the article DOI: 10.7150/ijbs.54014.].

Non-Covalent Interaction Enhancement on Active/Interfacial Layers via Two-Dimensional Vermiculite Doping for Efficient Organic Solar Cells.

Interface modification plays an important role in improving the power conversion efficiency (PCE) of organic solar cells (OSCs). However, the low non-covalent interaction between the cathode interface layer (CIL) and nonfullerene acceptor (NFA) directly affects the charge collection of OSCs. Here, the non-covalent interaction between the CIL and NFA is enhanced by introducing the 2D vermiculite (VML) in the poly(9,9-bis(3'-(N,N-dimethyl)-Nethylammonium-propyl-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)) dibromide (PFN-Br) interface layer to form an efficient electron transport channel. As a result, the electron extraction efficiency from the active layer to the CIL is increased, and the PCE of OSCs based on PBDB-T:ITIC is boosted from 10.87% to 12.89%. In addition, the strategy of CIL doping VML is proven to be universal in different CIL materials, for which the PCE is boosted from 10.21% to 11.57% for OSCs based on PDINN and from 9.82% to 11.27% for OSCs based on PNDIT-F3N. The results provide a viable option for designing efficient CIL for high-performance non-fullerene OSCs, which may promote the commercialization of OSCs.

Unconventional luminescent CS-PEC-based composite hemostasis sponge with antibacterial activity and visual monitoring for wound healing.

Multifunctional wound dressings are promising medical materials for various applications. Among them, dressings with antimicrobial activity, high biosafety, and real-time monitoring have attracted considerable research interest. Herein, a biodegradable hemostatic sponge comprising a chitosan skeleton and polyelectrolyte-surfactant complex (CS-PEC) was developed as a versatile wound dressing for wound pH monitoring and inhibition of bacterial infection. CS-PEC sponge with high porosity exhibited satisfactory fluid absorption capacity and biocompatibility, along with antibacterial properties against E. coli and S. aureus. In vivo experiments in rat liver trauma model revealed that wounds treated with the CS-PEC sponge recorded less blood loss (97.1 mg) and shorter hemostasis time (27.2 s) than those treated with commercial gelatin sponge (309.1 mg and 163.5 s, respectively). Furthermore, PECs based on unconventional luminescent molecules (L-C16-Hyp) were used as pH fluorescent indicators, which endowed the sponge with fluorescence-responsive behavior to wound pH changes in the range of 5.0-8.5. Visual images can be captured using a smartphone and converted to RGB color mode values for on-site assessment of wound status. This study sheds light on the design and application of unconventional luminescent materials in wound dressing and provides a smart and effective solution for wound management.

Clinical features of adult patients with allergic parotitis.

Background: Allergic parotitis (AP), due to its non-specific symptoms, frequently poses a diagnostic challenge, leading to cases being overlooked or misdiagnosed by clinicians. Objective: This study aimed to elucidate detailed clinical characteristics and common diagnostic indicators of AP. Methods: A comprehensive review and analysis of medical records was conducted from patients diagnosed with AP, encompassing demographic, clinical, and laboratory data, at the Affiliated Stomatological Hospital of Nanjing Medical University between January 2019 and March 2022. Results: The study enrolled 17 patients, evidenced by an average age of 36.00 ± 12.95 years. Common presentations of AP among the patients included notable symptoms such as parotid gland swelling, associated pain, and xerostomia. Ten patients had other atopic diseases. Palpation revealed the affected parotid glands to be soft and nodular, with an elevated local skin temperature. The unstimulated whole saliva flow rate was decreased. Ultrasonography demonstrated increased volume, reduced echo heterogeneity, and lymph node enlargement in the affected parotid glands. All cases observed increased serum salivary amylase and total IgE levels. Investigation of food allergens and inhaled allergen-specific IgE showed that all patients had suspected food allergies. Food provocation tests (FPT) induced AP in 13 cases, confirming the role of food allergens. Conclusion: Food allergens are involved in the etiology of AP, underscoring the importance of comprehensive clinical evaluation, including symptoms, signs, and confirmatory auxiliary tests, such as FPT, for accurate diagnosis and differentiation from other salivary gland pathologies.

Single Cobalt Ion-Immobilized Covalent Organic Framework for Lithium-Sulfur Batteries with Enhanced Rate Capabilities.

Covalent organic frameworks (COFs) are notable for their remarkable structure, function designability, and tailorability, as well as stability, and the introduction of "open metal sites" ensures the efficient binding of small molecules and activation of substrates for heterogeneous catalysis and energy storage. Herein, we use the postsynthetic metal sites to catalyze polysulfide conversion and to boost the binding affinity to active matter for lithium-sulfur batteries (LSBs). A dual-pore COF, USTB-27, with hxl topology has been successfully assembled from the imine chemical reaction between 2,3,8,9,14,15-hexa(4-formylphenyl)diquinoxalino [2,3-a:2',3'-c]phenazine and [2,2'-bipyridine]-5,5'-diamine. The chelating nitrogen sites of both modules are able to postsynthetically functionalize with single cobalt sites to generate USTB-27-Co. The discharge capacity of the sulfur-loaded S@USTB-27-Co composite in a LSB is 1063, 945, 836, 765, 696, and 644 mA h g-1 at current densities of 0.1, 0.2, 0.5, 1.0, 2.0, and 5.0 C, respectively, much superior to that of non-cobalt-functionalized species S@USTB-27. Following the increased current densities, the rate performance of S@USTB-27-Co is much better than that of S@USTB-27. In particular, the capacity retention at 5.0 C has a magnificent increase from 19% for the latter species to 61% for the former one. Moreover, S@USTB-27-Co exhibits a higher specific capacity of 543 mA h g-1 than that of S@USTB-27 (402 mA h g-1) at a current density of 1.0 C after electrochemical cycling for 500 runs. This work illustrates the "open metal sites" strategy to engineer the active chemical component conversion in COF channels as well as their binding strength for specific applications.

Identification of volatile compounds and their bioactivities from unpolar fraction of Alpinia oxyphylla Miq. and mining key genes of nootkatone biosynthesis.

In this study, analysis of the chemical constituents and bioactivities of the unpolar fractions [petroleum ether (PE) and chloroform (C)] of fruits and leaves of Alpinia oxyphylla Miq. were carried out, as well as the bioactivities of the main compounds nootkatone and valencene. From PE and C fractions of the fruits, and PE fraction of the leaves, 95.80%, 59.30%, and 82.11% of the chemical constituents respectively were identified by GC-MS. Among these identified compounds, nootkatone was the main compound in all of three fractions, while valencene was the second main compound in the PE fractions of the fruits and leaves. The bioactivities results showed that all of the fractions and the major compound nootkatone showed tyrosinase inhibitory, as well as inhibitory effect on NO production in LPS-stimulated RAW264.7 cells. While valencene only presented inhibitory activity on NO production in RAW264.7 cells. The critical genes involved in nootkatone biosynthesis in A. oxyphylla were identified from the public transcriptome datasets, and protein sequences were preliminarily analyzed. Our studies develop the usage of the unpolar fractions of A. oxyphylla, especially its leaves as the waste during its production, and meanwhile provide the gene resources for nootkatone biosynthesis.

The effects of propolis-loaded chitosan nanoparticles and menstrual blood stem cells on LPS-induced ovarian inflammation in the murine ovary in vivo: An in vitro and in vivo study.

Mammary glands infection via Gram-negative bacteria may cause infertility or reduced ovarian function. In the current study, a potential treatment for LPS-induced ovarian inflammation was developed. Propolis was loaded into chitosan nanoparticles and co-administered with menstrual blood stem cells (MenSCs) in mice infused with LPS. Various properties of propolis-loaded chitosan nanoparticles were evaluated using scanning electron microscopy, drug release assay, antibacterial assay, and radical scavenging assay. In vitro studies showed biocompatibility, anti-oxidative, and antibacterial properties of the developed propolis nanoformulation. In vivo study showed that mice treated with co-administration of propolis-loaded chitosan nanoparticles and MenSCs significantly increased the total ovarian follicle reserve in mice infused with LPS. Percentage of mature follicles in co-administration method was around 13.89 ± 1.72 %. Gene expression studies showed that the expression levels of inflammation related cytokines including IL6, IL8, IL-1ß, and TNF-α were downregulated in this group compared with other groups. However, the expression levels of PTEN, AKT, FOXO3 did not show a significant difference between groups. The developed treatment may potentially considered as an approach for treating ovarian infection with gram-negative bacteria.

Nanostructurally Engineering Covalent Organic Frameworks for Boosting CO2 Photoreduction.

Herein, a series of imine-linked covalent organic frameworks (COFs) are developed with advanced ordered mesoporous hollow spherical nanomorphology and ultra-large mesopores (4.6 nm in size), named OMHS-COF-M (M = H, Co, and Ni). The ordered mesoporous hollow spherical nanomorphology is revealed to be formed via an Ostwald ripening mechanism based on a one-step self-templated strategy. Encouraged by its unique structural features and outstanding photoelectrical property, the OMHS-COF-Co material is applied as the photocatalyst for CO2-to-CO reduction. Remarkably, it delivers an impressive CO production rate as high as 15 874 µmol g-1 h-1, a large selectivity of 92.4%, and a preeminent cycling stability. From in/ex situ experiments and density functional theory (DFT) calculations, the excellent CO2 photoreduction performance is ascribed to the desirable cooperation of unique ordered mesoporous hollow spherical host and abundant isolated Co active sites, enhancing CO2 activation, and improving electron transfer kinetics as well as reducing the energy barriers for intermediates *COOH generation and CO desorption.

Bioinspired Zn-MOF doped radial porous chitosan-based sponge with antibacterial and antioxidant properties for rapid hemostasis and wound healing.

Herein, a novel bioinspired radial porous zinc-based metal-organic framework (Zn-MOF) doped sodium alginate/chitosan derivatives/pullulan-based SA/PSCS/Pul/Zn-MOF (SPCP/Zn) composites sponge with excellent antioxidant and antibacterial properties was fabricated by the ice-templating method. Boric acid (BA) and Ca2+, which were respectively used as hydrogen- and ionic- bonding cross-linkers, provided strong mechanical properties for sponge matrix composed of SA, PSCS, and Pul. The obtained SPCP/Zn sponge exhibited uniform porous morphology, proper hydrophilicity, and admirable biocompatibility. In addition, the SPCP/Zn sponge achieved a sustained release of Zn2+ and gallic acid, which displayed powerful antibacterial and antioxidant activities. Importantly, the SPCP/Zn sponge exhibited shorter rapid hemostasis (20.4 ± 2.9 s) and lower blood loss (19.8 ± 4.3 mg). The SPCP/Zn sponge also showed faster wound closure ratio for the rat full-thickness skin defect model. It was revealed that SPCP/Zn sponge could significantly accelerate and enhance wound healing through downregulating inflammatory cytokines (TNF-α, IL-6) and increasing the expression of growth factors (VEGF). Due to its excellent properties, the SPCP/Zn sponge may have promising potential in wound healing applications.

Green Synthesis of PtPdNiFeCu High-Entropy Alloy Nanoparticles for Glucose Detection.

High-entropy alloys have long been used as a new type of alloy material and have attracted widespread concern because of their excellent performance, including their stable microstructure and particular catalytic properties. To design a safer preparation method, we report a novel approach targeting green synthesis, using tea polyphenols to prepare PtPdNiFeCu high-entropy alloy nanoparticles for glucose detection. The fabricated sensors were characterized by transmission electron microscopy and electrochemical experiments. Physical characterization showed that the nanoparticle has better dispersibility, and the average particle size is 7.5 nm. The electrochemical results showed that Tp-PtPdNiFeCu HEA-NPs had a high sensitivity of 1.264 µA mM-1 cm-2, a low detection limit of 4.503 µM, and a wide detection range of 0 - 10 mM. In addition, the sensor has better stability and selectivity for glucose detection.

Application of serum peptidomics for Parkinson's disease in SNCA-A30P mice.

Intraneuronal inclusions of alpha-synuclein (α-synuclein, α-syn) are commonly found in the brain of patients with Parkinson's disease (PD). The pathogenesis of the abundant α-syn protein in the blood has been extensively studied to understand its properties better. In recent years, peptidome analysis has received increasing attention. In this study, we identified and analyzed serum peptides from wild-type (WT) and the (Thy-1)-h[A30P] alpha-synuclein transgenic mice (SNCA-A30P mice) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). One thousand eight hundred fifty-six peptides from 771 proteins were analyzed. Among them, 151 peptides from 107 proteins were significantly differentially expressed. The glycoprotein VI platelet pathway (GP6) was the pathway's most significant differentially expressed signaling pathway. Cleavage sites of the differentially expressed peptides may reflect protease distribution and activity. We selected the most significantly differentially expressed peptide, VGGDPI, and found that it contained cathepsin K (Ctsk) and trypsin-1 cleavage sites, suggesting that Ctsk and trypsin-1 may be key peptidases in PD. α-syn is a protein associated with the pathogenesis of PD. mutations in several genes, including SNCA, which encodes α-syn, are associated with the development of PD. Bioinformatics analysis of the physiological pathways related to SNCA genes and apoptosis genes found the five most markedly up-regulated proteins: formin homology 2 domain-containing 1 (FHOD1), insulin receptor substrate 1(IRS1), TRPM8 channel-associated factor 1 (TCAF1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and interleukin-16 (IL-16). Therefore, the differentially expressed peptides in the five precursor protein domains may be potential bioactive peptides associated with α-syn and apoptosis. This study provides a validated peptidomics profile of SNCA-A30P mice and identifies potentially bioactive peptides linked to α-syn and apoptosis.

Leucine-rich repeat kinase 2 (LRRK2) inhibition upregulates microtubule-associated protein 1B to ameliorate lysosomal dysfunction and parkinsonism.

Mutations in LRRK2 (encoding leucine-rich repeat kinase 2 protein, LRRK2) are the most common genetic risk factors for Parkinson's disease (PD), and increased LRRK2 kinase activity was observed in sporadic PD. Therefore, inhibition of LRRK2 has been tested as a disease-modifying therapeutic strategy using the LRRK2 mutant mice and sporadic PD. Here, we report a newly designed molecule, FL090, as a LRRK2 kinase inhibitor, verified in cell culture and animal models of PD. Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice and SNCA A53T transgenic mice, FL090 ameliorated motor dysfunctions, reduced LRRK2 kinase activity, and rescued loss in the dopaminergic neurons in the substantia nigra. Notably, by RNA-Seq analysis, we identified microtubule-associated protein 1 (MAP1B) as a crucial mediator of FL090's neuroprotective effects and found that MAP1B and LRRK2 co-localize. Overexpression of MAP1B rescued 1-methyl-4-phenylpyridinium induced cytotoxicity through rescuing the lysosomal function, and the protective effect of FL090 was lost in MAP1B knockout cells. Further studies may be focused on the in vivo mechanisms of MAP1B and microtubule function in PD. Collectively, these findings highlight the potential of FL090 as a therapeutic agent for sporadic PD and familial PD without LRRK2 mutations.

Observation of Interpenetrated Topology Isomerism for Covalent Organic Frameworks with Atom-Resolution Single Crystal Structures.

Rational control and understanding of isomerism are of significance but still remain a great challenge in reticular frameworks, in particular, for covalent organic frameworks (COFs) due to the complicated synthesis and energy factors. Herein, reaction of 3,3',5,5'-tetra(4-formylphenyl)-2,2',6,6'-tetramethoxy-1,1'-biphenyl (TFTB) with 3,3',5,5'-tetrakis(4-aminophenyl)bimesityl (TAPB) under different reaction conditions affords single crystals of two 3D COF isomers, namely, USTB-20-dia and USTB-20-qtz. Their structures with resolutions up to 0.9-1.1 Å have been directly solved by three-dimensional electron diffraction (3D ED) and synchrotron single crystal X-ray diffraction, respectively. USTB-20-dia and USTB-20-qtz show rare 2 × 2-fold interpenetrated dia-b nets and 3-fold interpenetrated qtz-b frameworks. Comparative studies of the crystal structures of these COFs and theoretical simulation results indicate the crucial role of the flexible molecular configurations of building blocks in the present interpenetrated topology isomerism. This work not only presents the rare COF isomers but also gains an understanding of the formation of framework isomerism from both single crystal structures and theoretical simulation perspectives.

Cofacial porphyrin organic cages. Metals regulating excitation electron transfer and CO2 reduction electrocatalytic properties.

Herein, we introduce a comprehensive study of the photophysical behaviors and CO2 reduction electrocatalytic properties of a series of cofacial porphyrin organic cages (CPOC-M, M = H2, Co(ii), Ni(ii), Cu(ii), Zn(ii)), which are constructed by the covalent-bonded self-assembly of 5,10,15,20-tetrakis(4-formylphenyl)porphyrin (TFPP) and chiral (2-aminocyclohexyl)-1,4,5,8-naphthalenetetraformyl diimide (ANDI), followed by post-synthetic metalation. Electronic coupling between the TFPP donor and naphthalene-1,4 : 5,8-bis(dicarboximide) (NDI) acceptor in the metal-free cage is revealed to be very weak by UV-vis spectroscopic, electrochemical, and theoretical investigations. Photoexcitation of CPOC-H2, as well as its post-synthetic Zn and Co counterparts, leads to fast energy transfer from the triplet state porphyrin to the NDI unit according to the femtosecond transient absorption spectroscopic results. In addition, CPOC-Co enables much better electrocatalytic activity for CO2 reduction reaction than the other metallic CPOC-M (M = Ni(ii), Cu(ii), Zn(ii)) and monomeric porphyrin cobalt compartment, supplying a partial current density of 18.0 mA cm-2 at -0.90 V with 90% faradaic efficiency of CO.

Tau suppresses microtubule-regulated pancreatic insulin secretion.

Tau protein is implicated in the pathogenesis of Alzheimer's disease (AD) and other tauopathies, but its physiological function is in debate. Mostly explored in the brain, tau is also expressed in the pancreas. We further explored the mechanism of tau's involvement in the regulation of glucose-stimulated insulin secretion (GSIS) in islet ß-cells, and established a potential relationship between type 2 diabetes mellitus (T2DM) and AD. We demonstrate that pancreatic tau is crucial for insulin secretion regulation and glucose homeostasis. Tau levels were found to be elevated in ß-islet cells of patients with T2DM, and loss of tau enhanced insulin secretion in cell lines, drosophila, and mice. Pharmacological or genetic suppression of tau in the db/db diabetic mouse model normalized glucose levels by promoting insulin secretion and was recapitulated by pharmacological inhibition of microtubule assembly. Clinical studies further showed that serum tau protein was positively correlated with blood glucose levels in healthy controls, which was lost in AD. These findings present tau as a common therapeutic target between AD and T2DM.