Chemical characteristics and sources apportionment of volatile organic compounds in the primary urban area of Shijiazhuang, North China Plain.

VOCs (Volatile organic compounds) exert a vital role in ozone and secondary organic aerosol production, necessitating investigations into their concentration, chemical characteristics, and source apportionment for the effective implementation of measures aimed at preventing and controlling atmospheric pollution. From July to October 2020, online monitoring was conducted in the main urban area of Shijiazhuang to collect data on VOCs and analyze their concentrations and reactivity. Additionally, the PMF (positive matrix factorization) method was utilized to identify the VOCs sources. Results indicated that the TVOCs (total VOCs) concentration was (96.7 ± 63.4 µg/m3), with alkanes exhibiting the highest concentration of (36.1 ± 26.4 µg/m3), followed by OVOCs (16.4 ± 14.4 µg/m3). The key active components were alkenes and aromatics, among which xylene, propylene, toluene, propionaldehyde, acetaldehyde, ethylene, and styrene played crucial roles as reactive species. The sources derived from PMF analysis encompassed vehicle emissions, solvent and coating sources, combustion sources, industrial emissions sources, as well as plant sources, the contribution of which were 37.80%, 27.93%, 16.57%, 15.24%, and 2.46%, respectively. Hence, reducing vehicular exhaust emissions and encouraging neighboring industries to adopt low-volatile organic solvents and coatings should be prioritized to mitigate VOCs levels.

SGLT2 inhibitors ameliorate NAFLD in mice via downregulating PFKFB3, suppressing glycolysis and modulating macrophage polarization.

Sodium-glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i) is a novel class of anti-diabetic drug, which has displayed a promising benefit for non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effects of SGLT2i against NAFLD and the underlying mechanisms. The db/db mice and western diet-induced NAFLD mice were treated with dapagliflozin (1 mg·kg-1·d-1, i.g.) or canagliflozin (10 mg·kg-1·d-1, i.g.) for 8 weeks. We showed that the SGLT2i significantly improved NAFLD-associated metabolic indexes, and attenuated hepatic steatosis and fibrosis. Notably, SGLT2i reduced the levels of pro-inflammatory cytokines and chemokines, downregulated M1 macrophage marker expression and upregulated M2 macrophage marker expression in liver tissues. In cultured mouse bone marrow-derived macrophages and human peripheral blood mononuclear cell-derived macrophages, the SGLT2i (10, 20 and 40 µmol/L) significantly promoted macrophage polarization from M1 to M2 phenotype. RNA sequencing, Seahorse analysis and liquid chromatography-tandem mass spectrometry analysis revealed that the SGLT2i suppressed glycolysis and triggered metabolic reprogramming in macrophages. By using genetic manipulation and pharmacological inhibition, we identified that the SGLT2i targeted PFKFB3, a key enzyme of glycolysis, to modulate the macrophage polarization of M1 to M2 phenotype. Using a co-culture of macrophages with hepatocytes, we demonstrated that the SGLT2i inhibited lipogenesis in hepatocytes via crosstalk with macrophages. In conclusion, this study highlights a potential therapeutic application for repurposing SGLT2i and identifying a potential target PFKFB3 for NAFLD treatment.

Diverse BCR usage and T cell activation induced by different COVID-19 sequential vaccinations.

Limited knowledge is available on the differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibody breadth and T cell differentiation among different COVID-19 sequential vaccination strategies. In this study, we compared the immunogenicity of the third different dose of COVID-19 vaccines, such as mRNA (I-I-M), adenoviral vector (I-I-A), and recombinant protein (I-I-R) vaccines, in terms of the magnitude and breadth of antibody response and differentiation of SARS-CoV-2-specific T and B cells. These studies were performed in the same clinical trial, and the samples were assessed in the same laboratory. IGHV1-69, IGHV3-9, and IGHV4-34 were the dominant B cell receptor (BCR) usages of the I-I-M, I-I-A, and I-I-R groups, respectively; the RBD+ B cell activation capacities were comparable. Additionally, the I-I-R group was characterized by higher numbers of regulatory T cells, circulating T follicular helper cells (cTFH) - cTFH1 (CXRC3+CCR6-), cTFH1-17 (CXRC3+CCR6+), cTFH17 (CXRC3-CCR6+), and cTFH-CM (CD45RA-CCR7+), and lower SMNE+ T cell proliferative capacity than the other two groups, whereas I-I-A showed a higher proportion and number of virus-specific CD4+ T cells than I-I-R, as determined in ex vivo experiments. Our data confirmed different SARS-CoV-2-specific antibody profiles among the three different vaccination strategies and also provided insights regarding BCR usage and T/B cell activation and differentiation, which will guide a better selection of vaccination strategies in the future. IMPORTANCE: Using the same laboratory test to avoid unnecessary interference due to cohort ethnicity, and experimental and statistical errors, we have compared the T/B cell immune response in the same cohort sequential vaccinated by different types of COVID-19 vaccine. We found that different sequential vaccinations can induce different dominant BCR usage with no significant neutralizing titers and RBD+ B-cell phenotype. Recombinant protein vaccine can induce higher numbers of regulatory T cells, circulating TFH (CTFH)1, CTFH17, and CTFH-CM, and lower SMNE+ T-cell proliferative capacity than the other two groups, whereas I-I-A showed higher proportion and number of virus-specific CD4+ T cells than I-I-R. Overall, our study provides a deep insight about the source of differences in immune protection of different types of COVID-19 vaccines, which further improves our understanding of the mechanisms underlying the immune response to SARS-CoV-2.

(Phosphino)(stannyl)carbene.

The synthesis of a (phosphino)(stannyl)carbene is documented. The combination of phosphino and stannyl substituents imparts a highly ambiphilic nature to this carbene, enabling reactions with cyanide, isocyanide, and carbon monoxide. This leads to rare stannylketenimines and a stannylketene.

Tumor targeting peptide TMTP1 modified Antigen capture Nano-vaccine combined with chemotherapy and PD-L1 blockade effectively inhibits growth of ovarian cancer.

The mortality of ovarian cancer (OC) has long been the highest among gynecological malignancies. Although OC is considered to be an immunogenic tumor, the effect of immunotherapy is not satisfactory. The immunosuppressive microenvironment is one reason for this, and the absence of recognized effective antigens for vaccines is another. Chemotherapy, as one of the most commonly used treatment for OC, can produce chemotherapy-associated antigens (CAAs) during treatment and show the effect of in situ vaccine. Herein, we designed an antigen capture nano-vaccine NP-TP1@M-M with tumor targeting peptide TMTP1 and dendritic cell (DC) receptor mannose assembled on the surface and adjuvant monophosphoryl lipid A (MPLA) encapsulated in the core of poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA itself possessed the ability of antigen capture. TMTP1 was a tumor-homing peptide screened by our research team, which held extensive and excellent tumor targeting ability. After these modifications, NP-TP1@M-M could capture and enrich more tumor-specific antigens after chemotherapy, stimulate DC maturation, activate the adaptive immunity and combined with immune checkpoint blockade to maximize the release of the body's immune potential, providing an eutherapeutic strategy for the treatment of OC.

CpG Island Definition and Methylation Mapping of the T2T-YAO Genome.

Precisely defining and mapping all cytosine (C) positions and their clusters, known as CpG islands (CGIs), as well as their methylation status, are pivotal for genome-wide epigenetic studies, especially when population-centric reference genomes are ready for timely application. Here, we first align the two high-quality reference genomes, T2T-YAO and T2T-CHM13, from different ethnic backgrounds in a base-by-base fashion and compute their genome-wide density-defined and position-defined CGIs. Second, by mapping some representative genome-wide methylation data from selected organs onto the two genomes, we find that there are about 4.7%-5.8% sequence divergency of variable categories depending on quality cutoffs. Genes among the divergent sequences are mostly associated with neurological functions. Moreover, CGIs associated with the divergent sequences are significantly different with respect to CpG density and observed CpG/expected CpG (O/E) ratio between the two genomes. Finally, we find that the T2T-YAO genome not only has a greater CpG coverage than that of the T2T-CHM13 genome when whole-genome bisulfite sequencing (WGBS) data from the European and American populations are mapped to each reference, but also shows more hyper-methylated CpG sites as compared to the T2T-CHM13 genome. Our study suggests that future genome-wide epigenetic studies of the Chinese populations rely on both acquisition of high-quality methylation data and subsequent precision CGI mapping based on the Chinese T2T reference.

A Nanoconfined FeCo2O4-Embedded Ceramic Membrane Regulates Electron Transfer in Peroxymonosulfate Activation to Selectively Generate Singlet Oxygen for Water Decontamination.

Peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs), as a promising technology for water decontamination, are constrained by low reaction kinetics due to limited reaction selectivity and mass transfer. Herein, we designed a nanoconfined FeCo2O4-embedded ceramic membrane (FeCo2O4-CM) under flow-through pattern for PMS activation. Confining PMS and FeCo2O4 within nanochannels (3.0-4.7 nm) enhanced adsorption interactions (-7.84 eV vs -2.20 eV), thus boosting mass transfer. Nanoconfinement effect regulated electron transfer pathways from PMS to FeCo2O4-CM by modulating the active site transformation to ≡Co(III) in nanoconfined FeCo2O4-CM, enabling selectively generating 1O2. The primary role of 1O2 in the nanoconfined system was confirmed by kinetic solvent isotope experiments and indicative anthracene endoperoxide (DPAO2). The system enabled 100% removal of atrazine (ATZ) within a hydraulic retention time of 2.124 ms, demonstrating a rate constant over 5 orders of magnitude higher than the nonconfined system (3.50 × 103 s-1 vs 0.42 min-1). It also exhibited strong resilience to pH variations (3.3-9.0) and coexisting substances, demonstrating excellent stability indicated by consistent 100% ATZ removal for 14 days. This study sheds light on regulating electron transfer pathways to selectively generate 1O2 through the nanoconfinement effect, boosting the practical application of PMS-based AOPs in environmental remediation and potentially applying them to various other AOPs.

Pioglitazone alleviates lacrimal gland impairments induced by high-fat diet by suppressing M1 polarization.

A high-fat diet (HFD) contributes to the pathogenesis of various inflammatory and metabolic diseases. Previous research confirms that under HFD conditions, the extraorbital lacrimal glands (ELGs) can be impaired, with significant infiltration of pro-inflammatory macrophages (Mps). However, the relationship between HFD and Mps polarization in the ELGs remains unexplored. We first identified and validated the differential expression of PPAR-γ in murine ELGs fed ND and HFD through RNA sequencing. Tear secretion was measured using the Schirmer test. Lipid droplet deposition within the ELGs was observed through Oil Red O staining and transmission electron microscopy. Mps phenotypes were determined through quantitative RT-PCR, immunofluorescence, and flow cytometric analysis. An in vitro high-fat culture system for Mps was established using palmitic acid (PA), with supernatants collected for co-culture with lacrimal gland acinar cells. Gene expression was determined through ELISA, immunofluorescence, immunohistochemistry, quantitative RT-PCR, and Western blot analysis. Pioglitazone reduced M1-predominant infiltration induced by HFD by increasing PPAR-γ levels in ELGs, thereby alleviating lipid deposition and enhancing tear secretion. In vitro tests indicated that PPAR-γ agonist shifted Mps from M1-predominant to M2-predominant phenotype in PA-induced Mps, reducing lipid synthesis in LGACs and promoting lipid catabolism, thus alleviating lipid metabolic disorders within ELGs. Conversely, the PPAR-γ antagonist induced opposite effects. In summary, the lacrimal gland is highly sensitive to high-fat and lipid metabolic disorders. Downregulation of PPAR-γ expression in ELGs induces Mps polarization toward predominantly M1 phenotype, leading to lipid metabolic disorder and inflammatory responses via the NF-κb/ERK/JNK/P38 pathway.

Human-induced pluripotent stem cell-derived hepatocyte platform in modeling of SARS-CoV-2 infection.

Background and Aim: Currently, SARS-CoV-2 is still spreading rapidly and globally. A large proportion of patients with COVID-19 developed liver injuries. The human-induced pluripotent stem cell (iPSC)-derived hepatocytes recapitulate primary human hepatocytes and have been widely used in studies of liver diseases. Methods: To explore the susceptibility of hepatocytes to SARS-CoV-2, we differentiated iPSCs to functional hepatocytes and tried infecting them with different MOI (1, 0.1, 0.01) of SARS-CoV-2. Results: The iPSC-derived hepatocytes are highly susceptible to virus infection, even at 0.01 MOI. Other than the ancestral strain, iHeps also support the replication of SARS-CoV-2 variants including alpha, beta, theta, and delta. More interestingly, the ACE2 expression significantly upregulated after infection, suggesting a vicious cycle between virus infection and liver injury. Conclusions: The iPSC-derived hepatocytes can support the replication of SARS-CoV-2, and this platform could be used to investigate the SARS-CoV-2 hepatotropism and hepatic pathogenic mechanisms.

A crystalline stannyne.

The synthesis of heteronuclear alkyne analogues incorporating heavier group 14 elements (R1-C≡E-R2, E = Si, Ge, Sn, Pb) has posed a long-standing challenge. Neutral silynes (R1-C≡Si(L)-R2) and germynes (R1-C≡Ge(L)-R2) stabilized by a Lewis base have achieved sufficient stability for structural characterization at low temperatures. Here we show the isolation of a base-free stannyne (R1-C≡Sn-R2) at room temperature, achieved through the strategic use of a bulky cyclic phosphino ligand in combination with a bulky terphenyl substituent. Despite an allenic structure with strong delocalization of π-electrons, this compound exhibits adjacent ambiphilic carbon and tin centres, forming a carbon-tin multiple bond with ionic character. The stannyne demonstrates reactivity similar to carbenes or stannylenes, reacting with 1-adamantyl isocyanide and 2,3-dimethyl-1,3-butadiene. Additionally, its carbon-tin bond can be saturated by Et3N·HCl or cleaved by isopropyl isocyanate.

Ocular biometric characteristics of Han ethnicity in Tianjin and Uyghur ethnicity in Xinjiang undergoing cataract surgery.

AIM: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery. METHODS: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients. RESULTS: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P<0.001). After adjusting for age factors, Han patients had longer AL (23.51±1.05 vs 22.86±0.92 mm, P<0.001), deeper ACD (3.06±0.44 vs 2.97±0.37 mm, P=0.001), greater Kf (43.95±1.40 vs 43.42±1.69 D, P=0.001), steeper Ks (45.00±1.47 vs 44.26±1.71 D, P=0.001), and higher CA (1.04±0.68 vs 0.79±0.65, P=0.025) than Uyghur patients. Intra-ethnic male patients had longer AL, deeper ACD, and lower keratometry than female patients; however, CA between the sexes was almost similar. In the correlation analysis, we observed a positive correlation between AL and ACD in patients of both ethnicities (rHan =0.48, rUyghur =0.44, P<0.001), while AL was negatively correlated with Kf (rHan =-0.42, rUyghur =-0.64, P<0.001) and Ks (rHan =-0.38, rUyghur =-0.66, P<0.001). Additionally, Kf was positively correlated with Ks (rHan =0.89, rUyghur =0.93, P<0.001). CONCLUSION: There are differences in ocular biometric parameters between individuals of Han ethnicity in Tianjin and those of Uyghur ethnicity in Xinjiang undergoing cataract surgery. These ethnic variances can enhance our understanding of ocular diseases related to these parameters and provide guidance for surgical procedures.

Multifunctional elastomeric composites based on 3D graphene porous materials.

3D graphene porous materials (3GPM), which have low density, large porosity, excellent compressibility, high conductivity, hold huge promise for a wide range of applications. Nevertheless, most 3GPM have brittle and weak network structures, which limits their widespread use. Therefore, the preparation of a robust and elastic graphene porous network is critical for the functionalization of 3GPM. Herein, the recent research of 3GPM with excellent mechanical properties are summarized and the focus is on the effect factors that affect the mechanical properties of 3GPM. Moreover, the applications of elastic 3GPM in various fields, such as adsorption, energy storage, solar steam generation, sensors, flexible electronics, and electromagnetic wave shielding are comprehensively reviewed. At last, the new challenges and perspective for fabrication and functionalization of robust and elastic 3GPM are outlined. It is expected that the perspective will inspire more new ideas in preparation and functionalization of 3GPM.

Crocin's role in modulating MMP2/TIMP1 and mitigating hypoxia-induced pulmonary hypertension in mice.

To explore the molecular pathogenesis of pulmonary arterial hypertension (PAH) and identify potential therapeutic targets, we performed transcriptome sequencing of lung tissue from mice with hypoxia-induced pulmonary hypertension. Our Gene Ontology analysis revealed that "extracellular matrix organization" ranked high in the biological process category, and matrix metallopeptidases (MMPs) and other proteases also played important roles in it. Moreover, compared with those in the normoxia group, we confirmed that MMPs expression was upregulated in the hypoxia group, while the hub gene Timp1 was downregulated. Crocin, a natural MMP inhibitor, was found to reduce inflammation, decrease MMPs levels, increase Timp1 expression levels, and attenuate hypoxia-induced pulmonary hypertension in mice. In addition, analysis of the cell distribution of MMPs and Timp1 in the human lung cell atlas using single-cell RNAseq datasets revealed that MMPs and Timp1 are mainly expressed in a population of fibroblasts. Moreover, in vitro experiments revealed that crocin significantly inhibited myofibroblast proliferation, migration, and extracellular matrix deposition. Furthermore, we demonstrated that crocin inhibited TGF-ß1-induced fibroblast activation and regulated the pulmonary arterial fibroblast MMP2/TIMP1 balance by inhibiting the TGF-ß1/Smad3 signaling pathway. In summary, our results indicate that crocin attenuates hypoxia-induced pulmonary hypertension in mice by inhibiting TGF-ß1-induced myofibroblast activation.

Christensenella strain resources, genomic/metabolomic profiling, and association with host at species level.

The gut commensal bacteria Christensenellaceae species are negatively associated with many metabolic diseases, and have been seen as promising next-generation probiotics. However, the cultured Christensenellaceae strain resources were limited, and their beneficial mechanisms for improving metabolic diseases have yet to be explored. In this study, we developed a method that enabled the enrichment and cultivation of Christensenellaceae strains from fecal samples. Using this method, a collection of Christensenellaceae Gut Microbial Biobank (ChrisGMB) was established, composed of 87 strains and genomes that represent 14 species of 8 genera. Seven species were first described and the cultured Christensenellaceae resources have been significantly expanded at species and strain levels. Christensenella strains exerted different abilities in utilization of various complex polysaccharides and other carbon sources, exhibited host-adaptation capabilities such as acid tolerance and bile tolerance, produced a wide range of volatile probiotic metabolites and secondary bile acids. Cohort analyses demonstrated that Christensenellaceae and Christensenella were prevalent in various cohorts and the abundances were significantly reduced in T2D and OB cohorts. At species level, Christensenellaceae showed different changes among healthy and disease cohorts. C. faecalis, F. tenuis, L. tenuis, and Guo. tenuis significantly reduced in all the metabolic disease cohorts. The relative abundances of C. minuta, C. hongkongensis and C. massiliensis showed no significant change in NAFLD and ACVD. and C. tenuis and C. acetigenes showed no significant change in ACVD, and Q. tenuis and Geh. tenuis showed no significant change in NAFLD, when compared with the HC cohort. So far as we know, this is the largest collection of cultured resource and first exploration of Christensenellaceae prevalences and abundances at species level.

Effectiveness of the varicella vaccine in the real world, a matched case-control study.

BACKGROUND: Universal varicella vaccination has been introduced in many countries, but there are a number of important differences in their vaccination strategies. It is essential to establish a vaccination program that can maximize the benefits of varicella vaccine, but there is a lack of comprehensive research on the effectiveness of varicella vaccine in different vaccination status. METHODS: Using data from population-based surveillance platforms we conducted a 1:2 matched case-control study. The cases were clinically diagnosed varicella with onset from 2017 to 2021, 1-14 years old in Chaoyang District, Beijing. The controls were matched according to date of birth (±1 month), sex and residence. The vaccination data of the subjects were obtained from the Childhood Immunization Information Management System in Beijing. Using conditional logistic regression models with or without interaction terms, we evaluated the effectiveness of varicella vaccine in different vaccination status. RESULTS: A total of 2528 cases and 5056 controls were enrolled. This study found that whether the time since last vaccination was adjusted had a substantial effect on the comparing vaccine effectiveness (VE) between subgroups. After adjustment for the time since last vaccination, 1) the incremental VE of 2-dose was 49.6 % (95 % Confidence Interval [CI], 38.8-58.6) compared with 1-dose (93.9 % vs. 88.0 %); 2) Among children who received one dose, the risk of chickenpox in children vaccinated at 18-23 months was 1.382 (95 %CI, 1.084-1.762) times that in children vaccinated at 12-17 months. 3) the VE with less than one, two, and three year intervals is higher than that with six-year-intervals (P < 0.05), respectively. CONCLUSIONS: When comparing VE between subgroups of different vaccination status, the time since last vaccination should be adjusted. The first dose of varicella vaccine should be given as early as the second year of life, and the second dose can improve vaccine effectiveness.

Long Noncoding RNA MSL3P1 Regulates CUL3 mRNA Cytoplasmic Transport and Stability and Promotes Lung Adenocarcinoma Metastasis.

Lung adenocarcinoma (LUAD) is the most prevalent histological type of lung cancer. Previous studies have reported that specific long noncoding RNAs (lncRNA) are involved in cancer development and progression. The phenotype and mechanism of ENST00000440028, named MSL3P1, an lncRNA referred to as a cancer-testis gene with potential roles in tumorigenesis and progression, have not been reported. MSL3P1 is overexpressed in LUAD tumor tissues, which is significantly associated with clinical characteristics, metastasis, and poor clinical prognosis. MSL3P1 promotes the metastasis of LUAD in vitro and in vivo. The enhancer reprogramming in LUAD tumor tissue is the major driver of the aberrant expression of MSL3P1. Mechanistically, owing to the competitive binding to CUL3 mRNA with ZFC3H1 protein (a protein involved in targeting polyadenylated RNA to exosomes and promoting the degradation of target mRNA), MSL3P1 can prevent the ZFC3H1-mediated RNA degradation of CUL3 mRNA and transport it to the cytoplasm. This activates the downstream epithelial-to-mesenchymal transition signaling pathway and promotes tumor invasion and metastasis. Implications: This study indicates that lncRNA MSL3P1 regulates CUL3 mRNA stability and promotes metastasis and holds potential as a prognostic biomarker and therapeutic target in LUAD.

Correction: Recent advances in the chemistry of isolable carbene analogues with group 13-15 elements.

Correction for 'Recent advances in the chemistry of isolable carbene analogues with group 13-15 elements' by Mian He et al., Chem. Soc. Rev., 2024, https://doi.org/10.1039/D3CS00784G.

Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma.

BACKGROUND: Metabolic reprogramming and epigenetic alterations contribute to the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). Lactate-dependent histone modification is a new type of histone mark, which links glycolysis metabolite to the epigenetic process of lactylation. However, the role of histone lactylation in PDAC remains unclear. METHODS: The level of histone lactylation in PDAC was identified by western blot and immunohistochemistry, and its relationship with the overall survival was evaluated using a Kaplan-Meier survival plot. The participation of histone lactylation in the growth and progression of PDAC was confirmed through inhibition of histone lactylation by glycolysis inhibitors or lactate dehydrogenase A (LDHA) knockdown both in vitro and in vivo. The potential writers and erasers of histone lactylation in PDAC were identified by western blot and functional experiments. The potential target genes of H3K18 lactylation (H3K18la) were screened by CUT&Tag and RNA-seq analyses. The candidate target genes TTK protein kinase (TTK) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) were validated through ChIP-qPCR, RT-qPCR and western blot analyses. Next, the effects of these two genes in PDAC were confirmed by knockdown or overexpression. The interaction between TTK and LDHA was identified by Co-IP assay. RESULTS: Histone lactylation, especially H3K18la level was elevated in PDAC, and the high level of H3K18la was associated with poor prognosis. The suppression of glycolytic activity by different kinds of inhibitors or LDHA knockdown contributed to the anti-tumor effects of PDAC in vitro and in vivo. E1A binding protein p300 (P300) and histone deacetylase 2 were the potential writer and eraser of histone lactylation in PDAC cells, respectively. H3K18la was enriched at the promoters and activated the transcription of mitotic checkpoint regulators TTK and BUB1B. Interestingly, TTK and BUB1B could elevate the expression of P300 which in turn increased glycolysis. Moreover, TTK phosphorylated LDHA at tyrosine 239 (Y239) and activated LDHA, and subsequently upregulated lactate and H3K18la levels. CONCLUSIONS: The glycolysis-H3K18la-TTK/BUB1B positive feedback loop exacerbates dysfunction in PDAC. These findings delivered a new exploration and significant inter-relationship between lactate metabolic reprogramming and epigenetic regulation, which might pave the way toward novel lactylation treatment strategies in PDAC therapy.

Self-reporting electroswitchable colorimetric platform for smart ammonium recovery from wastewater.

Recovery of ammonium from wastewater represents a sustainable strategy within the context of global resource depletion, environmental pollution and carbon neutralization. The present study developed an advanced self-reporting electroswitchable colorimetric platform (SECP) to realize smart ammonium recovery based on the electrically stimulated transformation of Prussian blue/Prussian white (PB/PW) redox couple. The key to SECP was the selectivity of ammonium adsorption, sensitivity of desorption to electric signals and visualability of color change during switchable adsorption/desorption transformation. The results demonstrated the electrochemical intercalation-induced selective adsorption of NH4+ (selectivity coefficient of 3-19 versus other cations) and deintercalation-induced desorption on the PB-film electrode. At applied voltage of 1.2 V for 20 min, the negatively charged PB-film electrode achieved the maximum adsorption capacity of 3.2 mmol g-1. Reversing voltage to -0.2 V for 20 min resulted in desorption efficiency as high as 99%, indicating high adsorption/desorption reversibility and cyclic stability. The Fe(III)/Fe(II) redox dynamics were responsible for PB/PW transformation during reversible intercalation/deintercalation of NH4+. Based on the blue/transparence color change of PB/PW, the quantitative relationship was established between amounts of NH4+ adsorbed and extracted RGB values by multiple linear regression (R2 = 0.986, RMSE = 0.095). Then, the SECP was created upon the unique capability of real-time monitoring and feedback of color change of electrode to realize the automatic control of NH4+ adsorption/desorption. During five cycles of tests, the adsorption process consistently peaked at an average value of 3.15±0.04 mmol g-1, while desorption reliably approached the near-zero average of 0.06±0.04 mmol g-1. The average time of duration was 19.6±1.67 min for adsorption and 18.8±1.10 min for desorption, respectively. With electroswitchability, selectivity and self-reporting functionalities, the SECP represents a paradigm shift in smart ammonium recovery from wastewater, making wastewater treatment and resource recovery more efficient, more intelligent and more sustainable.