Integrated analysis of transcriptome and small RNAome reveals regulatory network of rapid and long-term response to heat stress in Rhododendron moulmainense.

MAIN CONCLUSION: The post-transcriptional gene regulatory pathway and small RNA pathway play important roles in regulating the rapid and long-term response of Rhododendron moulmainense to high-temperature stress. The Rhododendron plays an important role in maintaining ecological balance. However, it is difficult to domesticate for use in urban ecosystems due to their strict optimum growth temperature condition, and its evolution and adaptation are little known. Here, we combined transcriptome and small RNAome to reveal the rapid response and long-term adaptability regulation strategies in Rhododendron moulmainense under high-temperature stress. The post-transcriptional gene regulatory pathway plays important roles in stress response, in which the protein folding pathway is rapidly induced at 4 h after heat stress, and alternative splicing plays an important role in regulating gene expression at 7 days after heat stress. The chloroplasts oxidative damage is the main factor inhibiting photosynthesis efficiency. Through WGCNA analysis, we identified gene association patterns and potential key regulatory genes responsible for maintaining the ROS steady-state under heat stress. Finally, we found that the sRNA synthesis pathway is induced under heat stress. Combined with small RNAome, we found that more miRNAs are significantly changed under long-term heat stress. Furthermore, MYBs might play a central role in target gene interaction network of differentially expressed miRNAs in R. moulmainense under heat stress. MYBs are closely related to ABA, consistently, ABA synthesis and signaling pathways are significantly inhibited, and the change in stomatal aperture is not obvious under heat stress. Taken together, we gained valuable insights into the transplantation and long-term conservation domestication of Rhododendron, and provide genetic resources for genetic modification and molecular breeding to improve heat resistance in Rhododendron.

Catalytic Oxidation of Chlorobenzene over HSiW/CeO2 as a Co-Benefit of NOx Reduction: Remarkable Inhibition of Chlorobenzene Oxidation by NH3.

There is an urgent need to develop novel and high-performance catalysts for chlorinated volatile organic compound oxidation as a co-benefit of NOx. In this work, HSiW/CeO2 was used for chlorobenzene (CB) oxidation as a co-benefit of NOx reduction and the inhibition mechanism of NH3 was explored. CB oxidation over HSiW/CeO2 primarily followed the Mars-van-Krevelen mechanism and the Eley-Rideal mechanism, and the CB oxidation rate was influenced by the concentrations of surface adsorbed CB, Ce4+ ions, lattice oxygen species, gaseous CB, and surface adsorbed oxygen species. NH3 not only strongly inhibited CB adsorption onto HSiW/CeO2, but also noticeably decreased the amount of lattice oxygen species; hence, NH3 had a detrimental effect on the Mars-van-Krevelen mechanism. Meanwhile, NH3 caused a decrease in the amount of oxygen species adsorbed on HSiW/CeO2, which hindered the Eley-Rideal mechanism of CB oxidation. Hence, NH3 significantly hindered CB oxidation over HSiW/CeO2. This suggests that the removal of NOx and CB over this catalyst operated more like a two-stage process rather than a synergistic one. Therefore, to achieve simultaneous NOx and CB removal, it would be more meaningful to focus on improving the performances of HSiW/CeO2 for NOx reduction and CB oxidation separately.

Biomimetic leaves with immobilized catalase for machine learning-enabled validating fresh produce sanitation processes.

Washing and sanitation are vital steps during the postharvest processing of fresh produce to reduce the microbial load on the produce surface. Although current process control and validation tools effectively predict sanitizer concentrations in wash water, they have significant limitations in assessing sanitizer effectiveness for reducing microbial counts on produce surfaces. These challenges highlight the urgent need to improve the validation of sanitation processes, especially considering the presence of dynamic organic contaminants and complex surface topographies. This study aims to provide the fresh produce industry with a novel, reliable, and highly accurate method for validating the sanitation efficacy on the produce surface. Our results demonstrate the feasibility of using a food-grade, catalase (CAT)-immobilized biomimetic leaf in combination with vibrational spectroscopy and machine learning to predict microbial inactivation on microgreen surfaces. This was tested using two sanitizers: sodium hypochlorite (NaClO) and hydrogen peroxide (H2O2). The developed CAT-immobilized leaf-replicated PDMS (CAT@L-PDMS) effectively mimics the microscale topographies and bacterial distribution on the leaf surface. Alterations in the FTIR spectra of CAT@L-PDMS, following simulated sanitation processes, indicate chemical changes due to CAT oxidation induced by NaClO or H2O2 treatments, facilitating the subsequent machine learning modeling. Among the five algorithms tested, the competitive adaptive reweighted sampling partial least squares discriminant analysis (CARS-PLSDA) algorithm was the most effective for classifying the inactivation efficacy of E. coli on microgreen leaf surfaces. It predicted bacterial reduction on microgreen surfaces with 100% accuracy in both training and prediction sets for NaClO, and 95% in the training set and 86% in the prediction set for H2O2. This approach can improve the validation of fresh produce sanitation processes and pave the way for future research.

Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China.

BACKGROUND: Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. METHODS: VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. RESULTS: Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (ß = 0.6, 95%CI:0.1, 1.0; P = 0.01). CONCLUSIONS: The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04283799).

Lipidomics reveals the lipid metabolism disorders in Fructus Psoraleae-induced hepatotoxicity in rats with kidney-yin deficiency syndrome.

Fructus Psoraleae (FP), one of the important traditional Chinese medicines, is widely used in clinic and has been reported to be hepatotoxic. However, there is no report on the mechanism of FP-induced hepatotoxicity based on the theory of You Gu Wu Yun. In this study, plasma samples of rats with different kidney deficiency syndromes were investigated using a lipidomics approach based on UPLC/Q-TOF-MS technique. Firstly, multivariate statistical analysis, VIP value test, statistical test and other methods were used to find the lipid metabolites in the two syndrome model groups that were different from the normal group. The screening of differential lipid metabolites revealed that there were 12 biomarkers between the blank group and the kidney-yang deficiency model group as well as 16 differential metabolites between the kidney-yin deficiency model group, and finally a total of 17 relevant endogenous metabolites were identified, which could be used as differential lipid metabolites to distinguish between kidney-yin deficiency and kidney-yang deficiency evidence. Secondly, the relative content changes of metabolites in rats after administration of FP decoction were further compared to find the substances associated with toxicity after administration, and the diagnostic ability of the identified biomarkers was evaluated using a receiver operating characteristic curve (ROC). Results a total of 14 potential differential lipid metabolites, including LysoPC(20:0/0:0) and LysoPC(16:0/0:0), which may be related to hepatotoxicity in rats with kidney-yin deficiency syndrome were further screened, namely, the potential active lipid metabolites related to hepatotoxicity in rats induced by FP. Finally, cluster analysis, MetPA analysis and KEGG database were used to analyze metabolic pathways. It was discovered that the metabolism of glycerophospholipid and sphingolipid may be strongly related to the mechanism of hepatotoxicity brought on by FP. Overall, we described the lipidomics changes in rats treated with FP decoction and screened out 14 lipid metabolites related to hepatotoxicity in rats with kidney-yin deficiency, which served as a foundation for the theory of "syndrome differentiation and treatment" in traditional Chinese medicine and a guide for further investigation into the subsequent mechanism.

Plasmonic Terahertz Devices and Sensors Based on Carbon Electronics.

Tunable terahertz (THz) photonic devices are imperative in a wide range of applications ranging from THz signal modulation to molecular sensing. One of the currently prevailing methods is based on arrays of metallic or dielectric resonators integrated with functional materials in response to an external stimulus, in which for the purpose of sensing the external stimuli may introduce inadvertent undesirable effects into the target samples to be measured. Here we developed an alternative approach by postprocessing nanothickness macro-assembled graphene (nMAG) films with widely tunable THz conductivity, enabling versatile solid-state THz devices and sensors, showing multifunctional nMAG-based applications. The THz conductivities of free-standing nMAGs showed a broad range from 1.2 × 103 S/m in reduced graphene oxide before annealing to 4.0 × 106 S/m in a nMAG film annealed at 2800 °C. We fabricated nMAG/dielectric/metal and nMAG/dielectric/nMAG THz Salisbury absorbers with broad reflectance ranging from 0% to 80%. The highly conductive nMAG films enabled THz metasurfaces for sensing applications. Taking advantage of the resonant field enhancement arising from the plasmonic metasurface structures and the strong interactions between analyte molecules and nMAG films, we successfully detected diphenylamine with a limit of detection of 4.2 pg. Those wafer-scale nMAG films present promising potential in high-performance THz electronics, photonics, and sensors.

MYB30 integrates light signals with antioxidant biosynthesis to regulate plant responses during postsubmergence recovery.

Submergence is an abiotic stress that limits agricultural production world-wide. Plants sense oxygen levels during submergence and postsubmergence reoxygenation and modulate their responses. Increasing evidence suggests that completely submerged plants are often exposed to low-light stress, owing to the depth and turbidity of the surrounding water; however, how light availability affects submergence tolerance remains largely unknown. Here, we showed that Arabidopsis thaliana MYB DOMAIN PROTEIN30 (MYB30) is an important transcription factor that integrates light signaling and postsubmergence stress responses. MYB DOMAIN PROTEIN30 protein abundance decreased upon submergence and accumulated during reoxygenation. Under submergence conditions, CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), a central regulator of light signaling, caused the ubiquitination and degradation of MYB30. In response to desubmergence, however, light-induced MYB30 interacted with MYC2, a master transcription factor involved in jasmonate signaling, and activated the expression of the VITAMIN C DEFECTIVE1 (VTC1) and GLUTATHIONE SYNTHETASE1 (GSH1) gene families to enhance antioxidant biosynthesis. Consistent with this, the myb30 knockout mutant showed increased sensitivity to submergence, which was partially rescued by overexpression of VTC1 or GSH1. Thus, our findings uncover the mechanism by which the COP1-MYB30 module integrates light signals with cellular oxidative homeostasis to coordinate plant responses to postsubmergence stress.

Trust and the stock market reaction to lockdown and reopening announcements: A cross-country evidence.

We conduct a country-level analysis with a sample of 44 countries to examine whether generalised social trust has an impact on the stock market reaction to government announcements of lockdown and reopening during the COVID-19 pandemic. We first conduct an event study to measure the global stock markets' reaction to government announcements of lockdown and reopening, which is measured by each stock market's cumulative abnormal return. We then employ regression analysis to investigate the relationship between generalised social trust and the stock markets' reaction to government announcements of lockdown and reopening. The results show that government announcement of lockdown had a significant negative influence on most of the stock markets, whereas the magnitude of the stock markets' reaction to government announcement of reopening is relatively marginal, indicating a possible negative bias. Moreover, we find that generalised social trust is positively related to the stock markets' reaction to government announcement of lockdown and negatively related to the stock markets' reaction to government announcement of reopening.

Discovery and optimization of 4-anilinoquinazoline derivatives spanning ATP binding site and allosteric site as effective EGFR-C797S inhibitors.

Epidermal growth factor receptor (EGFR) is an effective drug target for the treatment of non-small cell lung cancer (NSCLC). However, a tertiary point mutation (C797S) at the ATP binding pocket of the EGFR induces resistance to the third-generation EGFR inhibitors, due to the loss of covalent interaction with Cys797. Here, we designed a series of 4-anilinoquinazoline derivatives that simultaneously occupied the ATP binding pocket and the allosteric site. The newly-synthesized compounds displayed high potency against EGFR-C797S resistance mutation. Among them, compound 14d presented high anti-proliferative effect against BaF3-EGFRL858R/T790M/C797S (IC50 = 0.75 µM) and BaF3-EGFR19del/T790M/C797S (IC50 = 0.09 µM) cells. Moreover, 14d resulted in obvious inhibition activities against EGFR and its downstream signaling pathways in a dose-dependent manner in BaF3-EGFR19del/T790M/C797S cells. Finally, 14d significantly inhibited tumor growth in BaF3-EGFR19del/T790M/C797S xenograft model (30 mg/kg, TGI = 67.95%). These results demonstrated that 14d is a novel and effective EGFR-C797S inhibitor which spanning the ATP binding pocket and the allosteric site and effective both in vitro and in vivo.

A Golgi-targeted viscosity rotor for monitoring early alcohol-induced liver injury.

We proposed to monitor the early stage of alcohol-induced liver injury through quantitatively detecting Golgi viscosity. Therefore, the first Golgi-targeted fluorescent rotor (GA-Vis) was developed. With the aid of GA-Vis, the changes in Golgi viscosity during alcohol-induced liver injury were quantitatively evaluated by fluorescence lifetime imaging in live cells and zebrafish. GA-Vis was qualified as a practical tool for future diagnoses of alcohol-induced liver injury.

The plant ESCRT component FREE1 regulates peroxisome-mediated turnover of lipid droplets in germinating Arabidopsis seedlings.

Lipid droplets (LDs) stored during seed development are mobilized and provide essential energy and lipids to support seedling growth upon germination. Triacylglycerols (TAGs) are the main neutral lipids stored in LDs. The lipase SUGAR DEPENDENT 1 (SDP1), which hydrolyzes TAGs in Arabidopsis thaliana, is localized on peroxisomes and traffics to the LD surface through peroxisomal extension, but the underlying mechanism remains elusive. Here, we report a previously unknown function of a plant-unique endosomal sorting complex required for transport (ESCRT) component FYVE DOMAIN PROTEIN REQUIRED FOR ENDOSOMAL SORTING 1 (FREE1) in regulating peroxisome/SDP1-mediated LD turnover in Arabidopsis. We showed that LD degradation was impaired in germinating free1 mutant; moreover, the tubulation of SDP1- or PEROXIN 11e (PEX11e)-marked peroxisomes and the migration of SDP1-positive peroxisomes to the LD surface were altered in the free1 mutant. Electron tomography analysis showed that peroxisomes failed to form tubules to engulf LDs in free1, unlike in the wild-type. FREE1 interacted directly with both PEX11e and SDP1, suggesting that these interactions may regulate peroxisomal extension and trafficking of the lipase SDP1 to LDs. Taken together, our results demonstrate a pivotal role for FREE1 in LD degradation in germinating seedlings via regulating peroxisomal tubulation and SDP1 targeting.

Mn2O3/Mn3O4-Cu1.5Mn1.5O4 spinel as an efficient Fenton-like catalyst activating persulfate for the degradation of bisphenol A: Superoxide radicals dominate the reaction.

In this work, a Mn2O3/Mn3O4-Cu1.5Mn1.5O4 spinel was fabricated and utilised as a catalyst to activate peroxydisulfate (PDS) leading to degradation of bisphenol A (BPA). The results showed that the system exhibited an excellent turnover frequency (TOF) of 2.7 × 10-3 s-1 and high stability. The amount of ion leaching was small and the degree of mineralisation was up to 66.2%. Superoxide radicals (O2-) were determined to be the dominant active species in the system. ≡Mn(II) and oxygen vacancies (Vo) were found to be the main active sites at the catalyst surface. The activation of PDS by the spinel catalyst and the reduction of dissolved oxygen both contributed to the production of O2- species. The synergistic effect of ≡Cu(I)/≡Cu(II) and ≡Mn(II)/≡Mn(III) redox pairs enabled the reaction to occur continuously. These results suggest the promise of this novel spinel catalyst in the removal of refractory organic compounds due to its excellent performance and stability. The catalyst may thus have great utility for environmental remediation.

Pesticide detection with covalent-organic-framework nanofilms at terahertz band.

Development of rapid molecular detection technologies is critical for the safer and smarter urban agriculture, medicine, and pro-environment. The emergent terahertz (THz) spectroscopy has its distinct advantages of being non-destructive, label-free and able to trace intermolecular and intramolecular vibrations, yet it suffers from the low performance of sensing materials available and their high fabrication cost. Here, we introduce a reticular material -- two dimensional (2D) covalent organic frameworks (COFs) and prepare their nanofilms as the lossy layer for THz absorbers. The COF film can be directly deposited on the dielectric layer of THz absorbers via an in-situ wet-chemistry growth. It possesses designable hierarchical structures, high specific areas of 736-971 m2/g, and precise nanopores of 1.6-2.1 nm, depending on its 2D COF constituents. The resulting THz absorber has been tested for pesticide detection. It presents a limit of detection at 2.2 ng and a selective response of 2.7-7.8 times that of interferents such as saccharides, antibiotics, and dyes, satisfying the need for practical application. Such flexible filmy sensor can measure the pesticide residue on the surface of apple for practical application. The THz sensor also demonstrates high stability over 1000 cycles of bending. Use of reticular nanofilm as the responsive layer may permit the future development of high-performance THz absorbers and other sensors for rapid molecular recognition.

Study on endocrine disruption effect of paclobutrazol and uniconazole on the thyroid of male and female rats based on lipidomics.

The present study investigated the effects of paclobutrazol and uniconazole on thyroid endocrine system in rats. Lipidomic analysis was performed to obtain the biomarkers of thyroid endocrine disruption induced by paclobutrazol and uniconazole. Network pharmacology was further used to discover potential targets of biomarkers related to drugs and diseases. After paclobutrazol and uniconazole administration, seven and four common biomarkers related to thyroid endocrine disruption for female and male rats were obtained, respectively. Paclobutrazol and uniconazole significantly increased the biomarker levels of PG (12:0/15:0), PS (14:0/16:0), PA (20:1/15:0) and PG (13:0/17:0) in both sexes of rats. Exposure to paclobutrazol additionally caused a significant decrease of PG (22:6/20:2), PE (24:1/18:1) and PE (24:0/18:0) in female rats, while an increase in male rats. Changes of the common biomarkers for paclobutrazol and uniconazole revealed similar endocrine disruption effect, which was higher in the females. Network pharmacology and KEGG pathway analysis indicated that the thyroid endocrine disrupting effects of paclobutrazol and uniconazole may be related to V-akt murine thymoma viral oncogene homolog (Akts), mitogen-activated protein kinase (MAPKs), epidermal growth factor receptor (EGFR), Insulin-like growth factor (IGF-1), IGF-IR and V-Raf murine sarcoma viral oncogene homolog B1 (BRAF). The results demonstrated that paclobutrazol and uniconazole could cause thyroid endocrine disorders in male and female rats, which were sex-specific, thus highlighting the importance of safe and effective application of these plant growth regulators.

Cross-Wavelength Hierarchical Metamaterials Enabled for Trans-Scale Molecules Detection Simultaneously.

Metamaterials have attracted increasing attention in sensing applications. However, the critical feature sizes of meta-atom span several orders of magnitude in length scale, almost all the metamaterials are designed to operate at limited bands. It is challenging for a single type of meta-atom with ultra-broadband adaptability. Inspired by the natural hierarchical architectures, herein, the authors introduce a new constructing scheme of cross-wavelength hierarchical metamaterials with a single type of meta-atom that can realize enhancement of terahertz (THz) resonance and surface-enhanced Raman scattering (SERS) at the same time. By combining multiple subwavelength structures at different hierarchical levels into a single meta-atom, the obtained metamaterial can operate in two frequencies and realize multiple functionalities. Armed with this hierarchical metamaterial, detecting analytes as small as sub-nanoscale chemical molecules or as big as microscale biomolecules simultaneously can be realized in one single metamaterial for the first time. As a proof-of-concept example, a smart sensory packaging is developed, which allowed them to real-time monitor the kinetic growth of pathogenic bacteria and their metabolites in food without opening the packaging. They believe that their work will provide a valuable example that satisfies the unmet need for multiscale functional meta-devices.

Postsynaptic Potential Energy as Determinant of Synaptic Plasticity.

Metabolic energy can be used as a unifying principle to control neuronal activity. However, whether and how metabolic energy alone can determine the outcome of synaptic plasticity remains unclear. This study proposes a computational model of synaptic plasticity that is completely determined by energy. A simple quantitative relationship between synaptic plasticity and postsynaptic potential energy is established. Synaptic weight is directly proportional to the difference between the baseline potential energy and the suprathreshold potential energy and is constrained by the maximum energy supply. Results show that the energy constraint improves the performance of synaptic plasticity and avoids setting the hard boundary of synaptic weights. With the same set of model parameters, our model can reproduce several classical experiments in homo- and heterosynaptic plasticity. The proposed model can explain the interaction mechanism of Hebbian and homeostatic plasticity at the cellular level. Homeostatic synaptic plasticity at different time scales coexists. Homeostatic plasticity operating on a long time scale is caused by heterosynaptic plasticity and, on the same time scale as Hebbian synaptic plasticity, is caused by the constraint of energy supply.

Djhsp70s, especially Djhsp70c, play a key role in planarian regeneration and tissue homeostasis by regulating cell proliferation and apoptosis.

Heat shock protein 70 family (HSP70s) is one of the most conserved and important group of HSPs as molecular chaperones, which plays an important role in cytoprotection, anti-apoptosis and so on. However, the molecular mechanism of HSP70s in animal regeneration remains to be delineated. In this study, we investigate the roles of HSP70s in regeneration of planarian. The four genes, Djhsp70a, Djhsp70b, Djhsp70c, and Djhsp70d of the HSP70s, are selected from the transcriptome database, because of their high expression levels in planarians. We then study the biological roles of each gene by conducting various experimental techniques, including RNAi, RT-PCR, WISH, Whole-mount immunostaining and TUNEL. The results show: (1) External stressors, such as temperature, tissue damage and ionic liquid upregulate the expression of Djhsp70s significantly. (2) The gene expression of Djhsp70s in planarians exhibits dynamic patterns. According to the result of WISH, the Djhsp70s are mainly expressed in parenchymal tissues on both sides of the body as well as blastema. It is consistent with the data of qRT-PCR. (3) After RNA interference of Djhsp70s, the worms experience cephalic regression and lysis, body curling, stagnant regeneration and death. (4) Knockdown of Djhsp70s affect the cell proliferation and apoptosis. These results suggest that Djhsp70s are not only conserved in cytoprotection, but involved in homeostasis maintenance and regeneration process by regulating coordination of cell proliferation and apoptosis in planarians.

Enhanced biogas biological upgrading from kitchen wastewater by in-situ hydrogen supply through nano zero-valent iron corrosion.

The in-situ hydrogen supply by nano zero-valent iron (nZVI, nFe0) corrosion provided a feasible way to improve the efficiency of biogas biological upgrading. This work studied the effects of nZVI at different dosages (0, 2, 4, 6, 8 and 10 g/L) on anaerobic digestion of kitchen wastewater by two buffer systems 2-[4-(2-hydroxyethyl) piperazin-1-yl] ethanesulfonic acid (HEPES) and sodium hydrogen carbonate (NaHCO3). The addition of nZVI improved the content of methane (CH4) and stability of anaerobic digestion process. In HEPES buffer system, the CH4 was all increased and the maximum reached 90.51% with 10 g/L nZVI, higher than 32.25% compared to the control. The maximum hydrogen enrichment (HE) was 113 ppb after nZVI addition, indicating the mass transfer efficiency of hydrogen (H2) was improved. Microbial community analysis showed that the total relative abundance of Methanobacterium and Methanolinea at 10 g/L nZVI was 53.72%, which was 1.62 times of the control group. However, in the NaHCO3 buffer system with 10 g/L nZVI addition, the content of CH4 and the loosely bound extracellular polymeric substances (LB-EPS) was lower than the control. The results indicated that the addition of nZVI was feasible for biogas upgrading, and the bidirectional effect of nZVI on the promotion or inhibition of bio-methanation might be related to the buffer system of the anaerobic process.

Discovery of Pteridine-7(8H)-one Derivatives as Potent and Selective Inhibitors of Bruton's Tyrosine Kinase (BTK).

Bruton's tyrosine kinase (BTK) is an attractive therapeutic target in the treatment of cancer, inflammation, and autoimmune diseases. Covalent and noncovalent BTK inhibitors have been developed, among which covalent BTK inhibitors have shown great clinical efficacy. However, some of them could produce adverse effects, such as diarrhea, rash, and platelet dysfunction, which are associated with the off-target inhibition of ITK and EGFR. In this study, we disclosed a series of pteridine-7(8H)-one derivatives as potent and selective covalent BTK inhibitors, which were optimized from 3z, an EGFR inhibitor previously reported by our group. Among them, compound 24a exhibited great BTK inhibition activity (IC50 = 4.0 nM) and high selectivity in both enzymatic (ITK >250-fold, EGFR >2500-fold) and cellular levels (ITK >227-fold, EGFR 27-fold). In U-937 xenograft models, 24a significantly inhibited tumor growth (TGI = 57.85%) at a 50 mg/kg dosage. Accordingly, 24a is a new BTK inhibitor worthy of further development.