Cysteine triggered cascade reaction forming coumarin: Visualization of cysteine fluctuation in alcoholic liver disease by a NIR fluorescent probe.

Alcoholic liver disease (ALD) is a chronic toxic liver injury caused by long-term heavy drinking. Due to the increasing incidence, ALD is becoming one of important medical tasks. Many studies have shown that the main mechanism of liver damage caused by large amounts of alcohol may be related to antioxidant stress. As an important antioxidant, cysteine (Cys) is involved in maintaining the normal redox balance and detoxifying metabolic function of the liver, which may be closely related to the pathogenesis of ALD. Therefore, it is necessary to develop a simple non-invasive method for rapid monitoring of Cys in liver. Thus, a near-infrared (NIR) fluorescent probe DCI-Ac-Cys which undergoes Cys triggered cascade reaction to form coumarin fluorophore is developed. Using the DCI-Ac-Cys, decreased Cys was observed in the liver of ALD mice. Importantly, different levels of Cys were monitored in the livers of ALD mice taking silybin and curcumin with the antioxidant effects, indicating the excellent therapeutic effect on ALD. This study provides the important references for the accurate diagnosis of ALD and the pharmacodynamic evaluation of silybin and curcumin in the treatment of ALD, and support new ideas for the pathogenesis of ALD.

Hybrid Overlayer of Defective Ni-MOF and NiO Nanoparticles toward Efficient TiO2/CdS Type-II Heterojunction.

The severe photocorrosion of cadmium sulfide (CdS) restricts its practical application for solar hydrogen production. Although remarkable progress has been achieved with an overlayer strategy for isolating the CdS surface, the lifetime of CdS-based photoanodes is still far from the actual requirements. Herein, a hybrid overlayer of defective Ni-MOF and NiO nanoparticles has been developed through the chemical bath deposition method with postannealing. This hybrid overlayer of Ni-MOF-d is coated on the surface of the TiO2/CdS type-II heterojunction. The composite photoanode exhibits a photocurrent density of 4.41 mA cm-2 at 1.23 VRHE, which is 3.47- and 1.32-fold that of CdS and TiO2/CdS, respectively. The Ni-MOF-d overlayer gives rise to a negative shift of the onset potential by 59.51 mV. After a long-term stability test of 11 h, a photocurrent retention of 70% is observed, which is among the most robust CdS-based photoanodes. The kinetics studies reveal that the performance improvements can be attributed to the multiple functions of the Ni-MOF-d hybrid overlayer, including isolating the CdS surface from the electrolyte, cocatalyzing the electrode oxidation processes, passivating the surface defect states of CdS, and facilitating the charge injection from the photoanode to the electrolyte.

Transition metals-based electrocatalysts on super-flat substrate for perovskite photovoltaic hydrogen production with 13.75% solar to hydrogen efficiency.

Harnessing the inexhaustible solar energy for water splitting is regarded one of the most promising strategies for hydrogen production. However, sluggish kinetics of oxygen evolution reaction (OER) and expensive photovoltaics have hindered commercial viability. Here, an adhesive-free electrodeposition process is developed for in-situ preparation of earth-abundant electrocatalysts on super-flat indium tin oxide (ITO) substrate. NiFe hydroxide exhibited prominent OER performance, achieving an ultra-low overpotential of 236 mV at 10 mA/cm2 in alkaline solution. With the superior OER activity, we achieved an unassisted solar water splitting by series connected perovskite solar cells (PSCs) of 2 cm2 aperture area with NiFe/ITO//Pt electrodes, yielding overall solar to hydrogen (STH) efficiency of 13.75 %. Furthermore, we upscaled the monolithic facility to utilize perovskite solar module for large-scale hydrogen production and maintained an approximate operating current of 20 mA. This creative strategy contributes to the decrease of industrial manufacturing expenses for perovskite-based photovoltaic-electrochemical (PV-EC) hydrogen production, further accelerating the conversion and utilization of carbon-free energy.

Ubiquitin ligase TRIM22 inhibits ovarian cancer malignancy via TCF4 degradation.

Ovarian cancer (OC) is one of the most common malignancies in women. Tripartite motif-containing protein 22 (TRIM22) plays an important role in the initiation and progression of malignant tumors. Similarly, the transcription factor 4 (TCF4) is an essential factor involved in the initiation and progression of many tumors. However, it is still unclear whether TRIM22 can affect TCF4 in OC. Therefore, this study aims to investigate the mechanism related to TRIM22 and TCF4 in OC. TRIM22 protein and mRNA levels were analyzed in samples from both clinical and cell lines. The effects of TRIM22 knockdown and overexpression on cell proliferation, colony formation, migration, invasion, and related biomarkers were evaluated. In addition, the role of ubiquitination-mediated degradation of TCF4 was investigated by qRT-PCR and Western blotting. The association between TRIM22 and TCF4 was evaluated by Western blotting, co-immunoprecipitation, proliferation, colony formation, invasion, migration, and related biomarkers. The results showed that the expression of TRIM22 was minimal in OC tissues. Furthermore, upregulation of TRIM22 significantly inhibited OC cell proliferation, colony formation, migration, and invasion. In addition, TRIM22 was observed to regulate the degradation of TCF4 through the ubiquitination pathway. TCF4 can reverse the effects of TRIM22 on proliferation, colony formation, migration, and invasion in OC cells. TRIM22-mediated ubiquitination of TCF4 at K48 is facilitated by the RING domain. Implications: In conclusion, ubiquitination of TCF4 protein in OC is regulated by TRIM22, which has the potential to limit the proliferation, migration, and invasion of OC.

Design, synthesis and biological evaluation of 4-(indolin-1-yl)-6-substituted-pyrido[3,2-d]pyrimidine derivatives as Mnk1/2 inhibitors.

The Mnk-eIF4E axis plays a crucial role in tumor development, and inhibiting Mnk kinases is a promising approach for cancer therapy. Starting with fragment WS23, a series of 4-(indolin-1-yl)-6-substituted-pyrido[3,2-d]pyrimidine derivatives were designed and synthesized. Among these derivatives, compound 15b showed the highest potency with IC50 values of 0.8 and 1.5 nM against Mnk1 and Mnk2, respectively. Additionally, it demonstrated good selectivity among 30 selected kinases. 15b significantly suppressed MOLM-13 and K562 cell lines growth and caused cell cycle arrest. Furthermore, the Western blot assay revealed that 15b effectively downregulated the downstream proteins p-eIF4E, Mcl-1, and c-myc. Additionally, 15b exhibited remarkable stability in rat plasma and rat and human microsomes. In vivo anti-tumor activity study suggested that treatment with 15b suppressed tumor growth in LL/2 syngeneic models. These findings highlight the potential of 15b as a novel and potent Mnks inhibitor, which deserves further investigation.

(-)-Epicatechin gallate ameliorates cyprodinil-induced cardiac developmental defects through inhibiting aryl hydrocarbon receptor in zebrafish.

BACKGROUND: Cyprodinil is a widely used fungicide with broad-spectrum activity, but it has been associated with cardiac abnormalities. (-)-Epicatechin gallate (ECG), a natural polyphenolic compound, has been shown to possess protective properties in cardiac development. METHODS: In this study, we investigated whether ECG could mitigate cyprodinil-induced heart defects using zebrafish embryos as a model. Zebrafish embryos were exposed to cyprodinil with or without ECG. RESULTS: Our results demonstrated that ECG significantly improved the survival rate, embryo movement, and hatching delay induced by cyprodinil. Furthermore, ECG effectively ameliorated cyprodinil-induced cardiac developmental toxicity, including pericardial anomaly and impairment of cardiac function. Mechanistically, ECG attenuated the cyprodinil-induced alterations in mRNA expression related to cardiac development, such as amhc, vmhc, tbx5, and gata4, as well as calcium ion channels, such as ncx1h, atp2a2a, and cdh2. Additionally, ECG was found to inhibit the activity of the aryl hydrocarbon receptor (AhR) signaling pathways induced by cyprodinil. CONCLUSIONS: In conclusion, our findings provide evidence for the protective effects of ECG against cyprodinil-induced cardiac developmental toxicity, mediated through the inhibition of AhR activity. These findings contribute to a better understanding of the regulatory mechanisms and safe utilization of pesticide, such as cyprodinil.

Engineering biomimetic nanosystem targeting multiple tumor radioresistance hallmarks for enhanced radiotherapy.

Tumor cells establish a robust self-defense system characterized by hypoxia, antioxidant overexpression, DNA damage repair, and so forth to resist radiotherapy. Targeting one of these features is insufficient to overcome radioresistance due to the feedback mechanisms initiated by tumor cells under radiotherapy. Therefore, we herein developed an engineering biomimetic nanosystem (M@HHPt) masked with tumor cell membranes and loaded with a hybridized protein-based nanoparticle carrying oxygens (O2) and cisplatin prodrugs (Pt(IV)) to target multiple tumor radioresistance hallmarks for enhanced radiotherapy. After administration, M@HHPt actively targeted and smoothly accumulated in tumor cells by virtue of its innate homing abilities to realize efficient co-delivery of O2 and Pt(IV). O2 introduction induced hypoxia alleviation cooperated with Pt(IV) reduction caused glutathione consumption greatly amplified radiotherapy-ignited cellular oxidative stress. Moreover, the released cisplatin effectively hindered DNA damage repair by crosslinking with radiotherapy-produced DNA fragments. Consequently, M@HHPt-sensitized radiotherapy significantly suppressed the proliferation of lung cancer H1975 cells with an extremely high sensitizer enhancement ratio of 1.91 and the progression of H1975 tumor models with an excellent tumor inhibition rate of 94.7%. Overall, this work provided a feasible strategy for tumor radiosensitization by overcoming multiple radioresistance mechanisms.

Tripartite motif family - its role in tumor progression and therapy resistance: a review.

PURPOSE OF REVIEW: In this review, we summarized published articles on the role of tripartite motif (TRIM) family members in the initiation and development of human malignancies. RECENT FINDINGS: The ubiquitin-proteasome system (UP-S) plays a critical role in cellular activities, and UP-S dysregulation contributes to tumorigenesis. One of the key regulators of the UP-S is the tripartite motif TRIM protein family, most of which are active E3 ubiquitin ligases. TRIM proteins are critical for the biological functions of cancer cells, including migration, invasion, metastasis, and therapy resistance. Therefore, it is important to understand how TRIM proteins function at the molecular level in cancer cells. SUMMARY: We provide a comprehensive and up-to-date overview about the role TRIMs play in cancer progression and therapy resistance. We propose TRIM family members as potential new markers and targets to overcome therapy failure.

Transcriptomic and metabolomic analysis reveals the influence of carbohydrates on lignin degradation mediated by Bacillus amyloliquefaciens.

Introduction: Ligninolytic bacteria can secrete extracellular enzymes to depolymerize lignin into small-molecular aromatics that are subsequently metabolized and funneled into the TCA cycle. Carbohydrates, which are the preferred carbon sources of bacteria, influence the metabolism of lignin-derived aromatics through bacteria. Methods: In this study, untargeted metabolomics and transcriptomics analyses were performed to investigate the effect of carbohydrates on lignin degradation mediated by Bacillus amyloliquefaciens MN-13, a strain with lignin-degrading activity that was isolated in our previous work. Results: The results demonstrated that the cell growth of the MN-13 strain and lignin removal were promoted when carbohydrates such as glucose and sodium carboxymethyl cellulose were added to an alkaline lignin-minimal salt medium (AL-MSM) culture. Metabolomics analysis showed that lignin depolymerization took place outside the cells, and the addition of glucose regulated the uptake and metabolism of lignin-derived monomers and activated the downstream metabolism process in cells. In the transcriptomics analysis, 299 DEGs were screened after 24 h of inoculation in AL-MSM with free glucose and 2 g/L glucose, respectively, accounting for 8.3% of the total amount of annotated genes. These DEGs were primarily assigned to 30 subcategories, including flagellar assembly, the PTS system, RNA degradation, glycolysis/gluconeogenesis, the TCA cycle, pyruvate metabolism, and tryptophan metabolism. These subcategories were closely associated with the cell structure, generation of cellular energy, and precursors for biosynthetic pathways, based on a - log 10 (P adjust) value in the KEGG pathway analysis. Conclusion: In summary, the addition of glucose increased lignin degradation mediated by the MN-13 strain through regulating glycolysis, TCA cycle, and central carbon metabolism.

Ruminal microbiota and muscle metabolome characteristics of Tibetan plateau yaks fed different dietary protein levels.

Introduction: The dietary protein level plays a crucial role in maintaining the equilibrium of rumen microbiota in yaks. To explore the association between dietary protein levels, rumen microbiota, and muscle metabolites, we examined the rumen microbiome and muscle metabolome characteristics in yaks subjected to varying dietary protein levels. Methods: In this study, 36 yaks were randomly assigned to three groups (n = 12 per group): low dietary protein group (LP, 12% protein concentration), medium dietary protein group (MP, 14% protein concentration), and high dietary protein group (HP, 16% protein concentration). Results: 16S rDNA sequencing revealed that the HP group exhibited the highest Chao1 and Observed_species indices, while the LP group demonstrated the lowest. Shannon and Simpson indices were significantly elevated in the MP group relative to the LP group (P < 0.05). At the genus level, the relative abundance of Christensenellaceae_R-7_group in the HP group was notably greater than that in the LP and MP groups (P < 0.05). Conversely, the relative abundance of Rikenellaceae_RC9_gut_group displayed an increasing tendency with escalating feed protein levels. Muscle metabolism analysis revealed that the content of the metabolite Uric acid was significantly higher in the LP group compared to the MP group (P < 0.05). The content of the metabolite L-(+)-Arabinose was significantly increased in the MP group compared to the HP group (P < 0.05), while the content of D-(-)-Glutamine and L-arginine was significantly reduced in the LP group (P < 0.05). The levels of metabolites 13-HPODE, Decanoylcarnitine, Lauric acid, L-(+)-Arabinose, and Uric acid were significantly elevated in the LP group relative to the HP group (P < 0.05). Furthermore, our observations disclosed correlations between rumen microbes and muscle metabolites. The relative abundance of NK4A214_group was negatively correlated with Orlistat concentration; the relative abundance of Christensenellaceae_R-7_group was positively correlated with D-(-)-Glutamine and L-arginine concentrations. Discussion: Our findings offer a foundation for comprehending the rumen microbiome of yaks subjected to different dietary protein levels and the intimately associated metabolic pathways of the yak muscle metabolome. Elucidating the rumen microbiome and muscle metabolome of yaks may facilitate the determination of dietary protein levels.

METTL3/YTHDF2 m6A axis mediates the progression of diabetic nephropathy through epigenetically suppressing PINK1 and mitophagy.

AIMS: This research aimed to investigate the specific mechanism of methyltransferase like 3 (METTL3) in the progression of diabetic kidney disease (DKD). MATERIALS AND METHODS: The model of diabetic kidney disease was established with HK-2 cells and mice in vitro and in vivo. The N6 methyladenosine (m6A) contents in the cells and tissues were detected with a commercial kit and the m6A levels of PTEN induced putative kinase 1 (PINK2) were detected with a MeRIP kit. The mRNA and protein levels were determined with RT-qPCR and western blot. The ROS, TNF-α, and IL-6 levels were assessed with ELISA. The cell proliferative ability was measured by a CCK-8 assay and cell apoptosis was determined with TUNEL staining. The HE and Masson staining was performed to observe the renal morphology. The RIP assay was conducted to detect the interaction between METTL3/YTHDF2 and PINK1. RESULTS: The m6A content and METTL3 levels were prominently elevated in diabetic kidney disease. METTL3 silencing promoted the cell growth and the expression of LC3 II, PINK1, and Parkin, while inhibiting the cell apoptosis and the expression of LC3 I and p62 in the high glucose (HG) stimulated HK-2 cells. METTL3 silencing also decreased the ROS, TNF-α, and IL-6 levels in diabetic kidney disease. PINK1 silencing neutralized the function of sh-METTL3 in the HG stimulated HK-2 cells. The HE and Masson staining showed that METTL3 silencing alleviated the kidney injury induced by DKD. METTL3 silencing decreased the m6A levels of PINK1, while increased the mRNA levels of PINK1 which depended on YTHDF2. CONCLUSIONS: METTL3 silencing could inhibit the progression of diabetic nephropathy in vivo and in vitro by regulating the m6A modification of PINK1, which depends on YTHDF2. Our research lays the theoretical foundation for the precise treatment of diabetic kidney disease and the development of targeted drugs in the future.

Tailoring the density of states of Ni(OH)2 with Ni0 towards solar urea wastewater splitting.

Solar urea wastewater splitting is capable of producing hydrogen and degrading the urea pollutant simultaneously. Nickel hydroxide (Ni(OH)2) has been recognized as an effective cocatalyst for the urea oxidation reaction (UOR). But the lack of an efficient preparation method and a suitable Ni(OH)2 based cocatalyst limits the performances of solar urea wastewater splitting. Herein, a potential-cycling method is developed with a high-purity nickel plate serving as the counter electrode and nickel source in a three-electrode configuration. Spherical Ni0-doped Ni(OH)2 nanoparticles are successfully synthesized on the surface of TiO2 nanorod arrays. The photocurrent density of TiO2/Ni0:Ni(OH)2 can reach 0.56 mA cm-2 at 1.23 VRHE in 1 M NaOH and 0.33 M CO(NH2)2 mixed electrolyte under AM1.5G illumination, which is 1.75 and 1.93 times those of TiO2/Ni(OH)2 deposited using a normal potentiostatic method with nickel salt solution and pristine TiO2, respectively. Ni0 doping can significantly decrease the charge transfer resistance and provide a more favorable distribution of density of states of Ni(OH)2 for the UOR. Furthermore, Ni0:Ni(OH)2 decorated TiO2 photoanodes exhibit good photocurrent retention during 12 h continuous testing. This work expands the preparation technique of urea catalysts and the strategy for developing highly efficient nickel-based catalysts.

Antibiotic intervention exacerbated oxidative stress and inflammatory responses in SD rats under hypobaric hypoxia exposure.

The gut microbiota plays a crucial role in maintaining host nutrition, metabolism, and immune homeostasis, particularly in extreme environmental conditions. However, the regulatory mechanisms of the gut microbiota in animal organisms hypobaric hypoxia exposure require further study. We conducted a research by comparing SD rats treated with an antibiotic (ABX) cocktail and untreated SD rats that were housed in a low-pressure oxygen chamber (simulating low pressure and hypoxic environment at 6000 m altitude) for 30 days. After the experiment, blood, feces, and lung tissues from SD rats were collected for analysis of blood, 16S rRNA amplicon sequencing, and non-targeted metabolomics. The results demonstrated that the antibiotic cocktail-treated SD rats exhibited elevated counts of neutrophil (Neu) and monocyte (Mon) cells, an enrichment of sulfate-reducing bacteria (SBC), reduced levels of glutathione, and accumulated phospholipid compounds. Notably, the accumulation of phospholipid compounds, particularly lysophosphatidic acid (LPA), lipopolysaccharide (LPS), and lysophosphatidylcholine (LPC), along with the aforementioned changes, contributed to heightened oxidative stress and inflammation in the organism. In addition, we explored the resistance mechanisms of SD rats in low-oxygen and low-pressure environments and found that increasing the quantity of the Prevotellaceae and related beneficial bacteria (especially Lactobacillus) could reduce oxidative stress and inflammation. These findings offer valuable insights into enhancing the adaptability of low-altitude animals under hypobaric hypoxia exposure.

Ruminal Fluid Transplantation Accelerates Rumen Microbial Remodeling and Improves Feed Efficiency in Yaks.

A relatively stable microbial ecological balance system in the rumen plays an important role in rumen environment stability and ruminant health maintenance. No studies have reported how rumen fluid transplantation (RFT) affects the composition of rumen microorganisms and yak growth performance. In this experiment, we transplanted fresh rumen fluid adapted to house-feeding yaks to yaks transitioned from natural pastures to house-feeding periods to investigate the effects of rumen fluid transplantation on rumen microbial community regulation and production performance. Twenty yaks were randomly divided into the control group (CON; n = 10) and the rumen fluid transplantation group (RT; n = 10). Ten yaks that had been adapted to stall fattening feed in one month were selected as the rumen fluid donor group to provide fresh rumen fluid. Ruminal fluid transplantation trials were conducted on the 1st, 3rd, and 5th. Overall, 1 L of ruminal fluid was transplanted to each yak in the RT and CON group. The formal trial then began with both groups fed the same diet. After this, growth performance was measured, rumen fluid was collected, and rumen microbial composition was compared using 16s rRNA sequencing data. The results showed that rumen fluid transplantation had no significant effect on yak total weight gain or daily weight gain (p > 0.05), and feed efficiency was higher in the RT group than in the CON group at 3 months (treatment × month: p < 0.01). Ruminal fluid transplantation significantly affected rumen alpha diversity (p < 0.05). Up to day 60, the RT group had significantly higher OTU numbers, Shannon diversity, and Simpson homogeneity than the CON group. Principal coordinate analysis showed that the rumen microbiota differed significantly on days 4 and 7 (p < 0.05). Bacteroidota, Firmicutes, Proteobacteria, and Spirochaetes were the most abundant phyla in the rumen. The relative abundances of Bacteroidota, Proteobacteria, and Spirochaetes were lower in the RT group than in the CON group, with a decrease observed in Bacteroidota in the RT group on days 7 and 28 after rumen fluid transplantation (p = 0.013), while Proteobacteria showed a decreasing trend in the CON group and an increasing trend in RT; however, this was only at day 4 (p = 0.019). The relative abundance of Firmicutes was significantly higher in the RT group than in the CON group on days 4, 7, and 28 (p = 0.001). Prevotella and Rikenellaceae_RC9_gut_group were the predominant genera. In conclusion, our findings suggest that rumen fluid transplantation improves yak growth performance and rumen microbial reshaping. The findings of this study provide new insights into yak microbial community transplantation and a reference for improving feed efficiency in the yak industry.

A Fluorescent Probe for Investigating the Role of Biothiols in Signaling Pathways Associated with Cerebral Ischemia-Reperfusion Injury.

Cerebral ischemia-reperfusion injury (CIRI) is intimately associated with the redox regulation of biothiol, a crucial antioxidant marker that precludes the onset of ROS. We designed a novel fluorescent probe, DCI-Ac-Py, showing various physicochemical properties, such as high selectivity, exceptional signal-to-noise ratio, near-infrared (NIR) optical window, and blood-brain barrier (BBB) penetrability, for detecting biothiols in the brain. The picolinate serves as a specific recognition group that is rapidly activated by biothiol and undergoes nucleophilic substitution with the adjacent acrylic ester to yield the desired NIR probe. Additionally, the probe's lipid solubility is improved through the inclusion of halogen atoms, which aids in penetrating the BBB. Using DCI-Ac-Py, we investigated changes of biothiols in vivo in the brains of mice during CIRI. We found that biothiol-mediated NF-kB classical (P65-related) and nonclassical (RelB-related) pathways contribute to abundant ROS production induced by CIRI and that biothiols are involved in redox regulation. These findings provide new insights into the study of CIRI and shed light on the physiological and pathological mechanisms of biothiols in the brain.

Evaluating high temperature photoelectrocatalysis of TiO2 model photoanode.

Sunlight concentration has been demonstrated as one promising strategy for practically photoelectrochemical (PEC) water splitting with exceeding 10% solar-to-hydrogen efficiency. However, the operating temperature of PEC devices, including the electrolyte and photoelectrodes, can be elevated to 65 ℃ naturally due to the concentrated sunlight and the thermal effect of near-infrared light. In this work, high temperature photoelectrocatalysis is evaluated using titanium dioxide (TiO2) photoanode as a model system, which is believed to be one of the most stable semiconductors. During the studied temperature range of 25-65 ℃, a linear increment of photocurrent density with a positive coefficient of 5.02 µA cm-2 K-1 can be observed. The onset potential for water electrolysis shows a significant negative shift by 200 mV. An amorphous titanium hydroxide layer and a number of oxygen vacancies generate on the surface of TiO2 nanorods, promoting the water oxidation kinetics. During long-term stability testing, the NaOH electrolyte degradation and TiO2 photocorrosion at high temperatures could cause the decaying photocurrent. This work evaluates the high temperature photoelectrocatalysis of TiO2 photoanode and reveals the mechanism of temperature effects on TiO2 model photoanode.

Multi-omics characterization of silent and productive HPV integration in cervical cancer.

Cervical cancer (CC) that is caused by high-risk human papillomavirus (HPV) remains a significant public health problem worldwide. HPV integration sites can be silent or actively transcribed, leading to the production of viral-host fusion transcripts. Herein, we demonstrate that only productive HPV integration sites were nonrandomly distributed across both viral and host genomes, suggesting that productive integration sites are under selection and likely to contribute to CC pathophysiology. Furthermore, using large-scale, multi-omics (clinical, genomic, transcriptional, proteomic, phosphoproteomic, and single-cell) data, we demonstrate that tumors with productive HPV integration are associated with higher E6/E7 proteins and enhanced tumor aggressiveness and immunoevasion. Importantly, productive HPV integration increases from carcinoma in situ to advanced disease. This study improves our understanding of the functional consequences of HPV fusion transcripts on the biology and pathophysiology of HPV-driven CCs, suggesting that productive HPV integration should be evaluated as an indicator of high risk for progression to aggressive cancers.

Ring-Opening Oligomerization Mechanism of a Vanillin-Furfurylamine-Based Benzoxazine and a Mono-Azomethine Derivative.

Exploring the ring-opening polymerization (ROP) mechanism of benzoxazines is a fundamental issue in benzoxazine chemistry. Though some research papers on the topic have been reported, the ROP mechanism of mono-benzoxazines is still elusive. The key point for mechanistic studies is to determine and characterize the structure and formation pathways of the products generated in ROP. In this paper, the ROP of a vanillin-furfurylamine-based benzoxazine and a mono-azomethine derivative is studied with differential scanning calorimetry, fourier transform infrared spectroscopy, nuclear magnetic resonance, and electrospray ionization mass spectrometry, respectively. The results show that the products consist of a range of cationic species, zwitterions, fragments, and series of cyclic and linear oligomers of varying molecular sizes. It is proposed that both mono-benzoxazines undergo thermally activated cationic ring-opening oligomerization via zwitterion intermediates. Upon thermal induction, multi-bond-cleavage takes place to form various zwitterionic intermediates, which react with a monomer, a fragment, or a second zwitterion by several pathways to generate cyclic and linear oligomers.

Evaluation of application potential of dye-decolorizing peroxidase from Bacillus amyloliquefaciens in bioremediation of paper and pulp mill effluent.

Pulp and paper mill effluent is rich in recalcitrant and toxic pollutants compounds and causes pollution. To find an efficient biocatalyst for the treatment of effluent, a dye-decolorizing peroxidase from Bacillus amyloliquefaciens MN-13, which is capable of degrading lignin, was used for the bioremediation of paper and pulp mill effluent. The dye-decolorizing peroxidase from Bacillus amyloliquefaciens (BaDyP) exhibited high-redox potential to 2, 2'-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) ammonium salt (ABTS), veratryl alcohol, Mn2+, reactive blue 19, reactive black 5 and lignin dimer guaiacylglycerol-beta-guaiacyl ether (GGE). When GGE was used as substrate, BaDyP broke ß-O-4 bond of GGE and then oxidize Cα to generate vanillin. The Km values for ABTS and veratryl alcohol were 2.19 mm and 0.07 mm, respectively. The Vmax for ABTS and veratryl alcohol were 1.8 mm/min and 14.12 mm/min, respectively. The BaDyP-mediated treatment of pulp and paper mill effluent led to significant reduction of chemical oxygen demand (COD) and color. When 5% (v/v) of effluent was treated with BaDyP for 12 h at 30°C and pH 2, the removal of COD, color, and lignin was achieved at 82.7, 80.2, and 78.20%, respectively. In detoxification assay, the seeds of Vigna unguiculata grown in treated effluent showed a significant increase in germination rate from 66.7% (untreated effluent) to 90%, and in radicle length from 0.68 cm (untreated effluent) to 1.26 cm, respectively. In the meanwhile, the inhibition of Escherichia coli and Bacillus subtilis by the treated effluent reduced significantly as compared to untreated effluent, indicating high detoxification performance of BaDyP for the treatment of pulp and paper mill effluent. The findings suggest that BaDyP is a potential catalyst for bioremediation of pulp and paper mill effluent, as it is effective in substantial lowering of pollutants load as well as reduces COD, color, and toxicity of effluent.

Effects of high concentrate rations on ruminal fermentation and microbiota of yaks.

Ruminal microflora is closely correlated with the ruminant's diet. However, information regarding the effect of high concentrate diets on rumen microflora in yaks is lacking. In the current study, 24 healthy male yaks were randomly assigned to two groups, each fed with different diets: less concentrate (LC; concentrate: coarse = 40: 60) and high concentrate (HC; concentrate: coarse = 80: 20) diets. Subsequently, a 21-day feeding trial was performed with the yaks, and rumen fluid samples were collected and compared using 16 s rRNA sequencing. The results showed that NH3-N, total VFA, acetate, butyrate, isobutyrate, and isovalerate were significantly higher in the HC group than that in the LC group (p < 0.05), while microbial diversity and richness were significantly lower in the HC group (p < 0.05). Principal coordinate analysis indicated that rumen microflora was significantly different in LC and HC groups (p < 0.05). In the rumen, phyla Firmicutes and Bacteroidota were the most abundant bacteria, with Firmicutes being more abundant, and Bacteroidota being less abundant in the HC group than those found in the LC group. Christensenellaceae_R-7_group and Prevotella are the highest abundant ones at the genus level. The relative abundance of Acetitomaculum, Ruminococcus, and Candidatus_Saccharimonas were significantly higher in the HC group than that in the LC group (p < 0.05), while the relative abundance of Olsenella was significantly lower in the HC group than in the LC group (p < 0.05). Compared to the LC group, the relative abundance of Prevotella, Ruminococcus, and Candidatus_Saccharimonas was significantly higher in the HC group. The relative abundances of Prevotella, Prevotellaceae_UCG-003, Olsenella, Ruminococcus, Acetitomaculum, Candidatus_Saccharimonas, and NK4A214_group were correlated with ruminal fermentation parameters (p < 0.05). Furthermore, PICRUSt 2 estimation indicated that microbial genes associated with valine, leucine, and isoleucine biosynthesis were overexpressed in the rumen microflora of yaks in the HC group (p < 0.05). Conclusively, our results suggest that high concentrate diets affect the microflora composition and fermentation function in yak rumen. The present findings would provide new insights into the health of yaks under high concentrate feeding conditions and serve as a potent reference for the short-term fattening processes of yaks.