Arsinothricin Biosynthesis Involving a Radical SAM Enzyme for Noncanonical SAM Cleavage and C-As Bond Formation.

Arsinothricin is a potent antibiotic secreted by soil bacteria. The biosynthesis of arsinothricin was proposed to involve a C-As bond formation between trivalent As and the 3-amino-3-carboxypropyl (ACP) group of S-adenosyl-l-methionine (SAM), which is catalyzed by the protein ArsL. However, ArsL has not been characterized in detail. Interestingly, ArsL contains a CxxxCxxC motif and thus belongs to the radical SAM enzyme superfamily, the members of which cleave SAM and generate a 5'-deoxyadenosyl radical. Here, we found that ArsL cleaves the Cγ,Met-S bond of SAM and generates an ACP radical that resembles Dph2, a noncanonical radical SAM enzyme involved in diphthamid biosynthesis. As Dph2 does not contain the CxxxCxxC motif, ArsL is a unique radical SAM enzyme that contains this motif but generates a noncanonical ACP radical. Together with the methyltransferase ArsM, we successfully reconstituted arsinothricin biosynthesis in vitro. ArsL has a conserved RCCLKC motif in the C-terminal sequence and belongs to the RCCLKC-tail radical SAM protein subfamily. By truncation and mutagenesis, we showed that this motif plays an important role in binding to the substrate arsenite and is highly important for its activity. Our results suggested that ArsL has a canonical radical SAM enzyme motif but catalyzes a noncanonical radical SAM reaction, implying that more noncanonical radical SAM chemistry may exist within the radical SAM enzyme superfamily.

Establishment of diagnostic model and identification of diagnostic markers between liver cancer and cirrhosis based on multi-chip and machine learning.

OBJECTIVE: Most cases of hepatocellular carcinoma (HCC) arise as a consequence of cirrhosis. In this study, our objective is to construct a comprehensive diagnostic model that investigates the diagnostic markers distinguishing between cirrhosis and HCC. METHODS: Based on multiple GEO datasets containing cirrhosis and HCC samples, we used lasso regression, random forest (RF)-recursive feature elimination (RFE) and receiver operator characteristic analysis to screen for characteristic genes. Subsequently, we integrated these genes into a multivariable logistic regression model and validated the linear prediction scores in both training and validation cohorts. The ssGSEA algorithm was used to estimate the fraction of infiltrating immune cells in the samples. Finally, molecular typing for patients with cirrhosis was performed using the CCP algorithm. RESULTS: The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model. In both the training and validation cohorts, the model exhibited an area under the curve (AUC) greater than 0.9 and a kappa value of approximately 0.9. Additionally, the calibration curve demonstrated excellent concordance between observed and predicted incidence rates. Comparatively, HCC displayed overall downregulation of infiltrating immune cells compared to cirrhosis. Notably, CCBE1 showed strong correlations with the tumour immune microenvironment as well as genes associated with cell death and cellular ageing processes. Furthermore, cirrhosis subtypes with high linear predictive scores were enriched in multiple cancer-related pathways. CONCLUSION: In conclusion, we successfully identified diagnostic markers distinguishing between cirrhosis and hepatocellular carcinoma and developed a novel diagnostic model for discriminating the two conditions. CCBE1 might exert a pivotal role in regulating the tumour microenvironment, cell death and senescence.

Rich Sulfur Vacancies and Reduced Schottky Barrier Height Synergistically Enable Au/ZnIn2S4 with Enhanced Photocatalytic CO2 Reduction into CO.

Constructing the plasmonic metal/semiconductor heterostructure with a suitable Schottky barrier height (SBH) and the sufficiently reliable active sites is of importance to achieve highly efficient and selective photocatalytic CO2 reduction into hydrocarbon fuels. Herein, we report Au/sulfur vacancy-rich ZnIn2S4 (Au/VSR-ZIS) hierarchical photocatalysts, fabricated via in situ photodepositing Au nanoparticles (NPs) onto the nanosheet self-assembled ZnIn2S4 (ZIS) micrometer flowers (MFs) with rich sulfur vacancies (VS). Density functional theory (DFT) calculations confirm that for the Au/VSR-ZIS system, the Au NPs serve as the reaction sites for H2O oxidation, and the VSR-ZIS MFs serve as those for CO2 reduction. The rich VS in the Au/VSR-ZIS hybrid can reduce its SBH so as to boost more hot electrons in the Au NPs across its Schottky barrier and then inject into the conduction band (CB) of the VSR-ZIS MFs. In addition, VS can also act as the electron sink to trap the photogenerated electrons, retarding the recombination of photogenerated carriers. The two merits effectively enhance the photogenerated electron density in the surface of VSR-ZIS MFs, availing CO2 photoreduction. In addition, the introduction of rich VS in the Au/VSR-ZIS hybrid can offer more active sites, benefiting the CO2 adsorption and accelerating the desorption of CO* from the surface of the photocatalyst. Therefore, under visible light illumination with no sacrificial reagent, the optimum photocatalyst (Au/VSR-ZIS-0.4) presents the enhanced and selective CO2 photoreduction into CO (8.15 µmol g-1h-1 and near 100%), which are superior to those of most of ZIS-based and plasmon-based photocatalysts. The photocatalytic activity is about 40.0-fold as high as that of the Vs-poor-ZIS (VSP-ZIS) MFs. This work contributes a viable strategy for designing highly efficient plasmonic photocatalysts by using the synergism of the anion vacancies and the optimized SBH induced by them.

Discovery of a prominent dual-target DDR1/EGFR inhibitor aimed DDR1/EGFR-positive NSCLC.

This study aimed to develop the first dual-target small molecule inhibitor concurrently targeting Discoidin domain receptor 1 (DDR1) and Epidermal growth factor receptor (EGFR), which play a crucial interdependent roles in non-small cell lung cancer (NSCLC), demonstrating a synergistic inhibitory effect. A series of innovative dual-target inhibitors for DDR1 and EGFR were discovered. These compounds were designed and synthesized using structural optimization strategies based on the lead compound BZF02, employing 4,6-pyrimidine diamine as the core scaffold, followed by an investigation of their biological activities. Among these compounds, D06 was selected and showed micromolar enzymatic potencies against DDR1 and EGFR. Subsequently, compound D06 was observed to inhibit NSCLC cell proliferation and invasion. Demonstrating acceptable pharmacokinetic performance, compound D06 exhibited its anti-tumor activity in NSCLC PC-9/GR xenograft models without apparent toxicity or significant weight loss. These collective results showcase the successful synthesis of a potent dual-targeted inhibitor, suggesting the potential therapeutic efficacy of co-targeting DDR1 and EGFR for DDR1/EGFR-positive NSCLC.

Bacmethy: A novel and convenient tool for investigating bacterial DNA methylation pattern and their transcriptional regulation effects.

DNA methylation serves as the primary mode of epigenetic regulation in prokaryotes, particularly through transcriptional regulation. With the rapid implementation of third-generation sequencing technology, we are currently experiencing a golden age of bacterial epigenomics. However, there has been a lack of comprehensive research exploring the versatility and consequential impact of bacterial DNA methylome on cellular and physiological functions. There is a critical need for a user-friendly bioinformatics tool that can effectively characterize DNA methylation modification features and predict the regulation patterns. To address this gap, the current study introduces Bacmethy, an innovative tool that utilizes SMRT-seq data and offers a range of analytical modules. First, the tool classifies methylation sites in the genome, highlighting the distinct regulations present under varying modification fractions and location enrichment. Furthermore, this tool enables us to identify regulatory region methylation and potential cis and trans interactions between methylation sites and regulatory effectors. Using benchmark data sets and our data, we show that our tool facilitates the understanding of the distinctive traits of DNA methylation modifications and predicts transcriptional regulation effects on important physiological and pathological functions. Bacmethy code is freely available, and the Docker image is downloadable. Bacmethy has been made available as a user-friendly web server interface at https://bacmethy.med.sustech.edu.cn.

Inhibition mechanisms of CRISPR-Cas9 by AcrIIA25.1 and AcrIIA32.

In the ongoing arms race between bacteria and bacteriophages, bacteriophages have evolved anti-CRISPR proteins to counteract bacterial CRISPR-Cas systems. Recently, AcrIIA25.1 and AcrIIA32 have been found to effectively inhibit the activity of SpyCas9 both in bacterial and human cells. However, their molecular mechanisms remain elusive. Here, we report the cryo-electron microscopy structures of ternary complexes formed by AcrIIA25.1 and AcrIIA32 bound to SpyCas9-sgRNA. Using structural analysis and biochemical experiments, we revealed that AcrIIA25.1 and AcrIIA32 recognize a novel, previously-unidentified anti-CRISPR binding site on SpyCas9. We found that both AcrIIA25.1 and AcrIIA32 directly interact with the WED domain, where they spatially obstruct conformational changes of the WED and PI domains, thereby inhibiting SpyCas9 from recognizing protospacer adjacent motif (PAM) and unwinding double-stranded DNA. In addition, they may inhibit nuclease activity by blocking the dynamic conformational changes of the SpyCas9 surveillance complex. In summary, our data elucidate the inhibition mechanisms of two new anti-CRISPR proteins, provide new strategies for the modulation of SpyCas9 activity, and expand our understanding of the diversity of anti-CRISPR protein inhibition mechanisms.

Room-Temperature Band-Aligned Infrared Heterostructures for Integrable Sensing and Communication.

The demand for miniaturized and integrated multifunctional devices drives the progression of high-performance infrared photodetectors for diverse applications, including remote sensing, air defense, and communications, among others. Nonetheless, infrared photodetectors that rely solely on single low-dimensional materials often face challenges due to the limited absorption cross-section and suboptimal carrier mobility, which can impair sensitivity and prolong response times. Here, through experimental validation is demonstrated, precise control over energy band alignment in a type-II van der Waals heterojunction, comprising vertically stacked 2D Ta2NiSe5 and the topological insulator Bi2Se3, where the configuration enables polarization-sensitive, wide-spectral-range photodetection. Experimental evaluations at room temperature reveal that the device exhibits a self-powered responsivity of 0.48 A·W-1, a specific directivity of 3.8 × 1011 cm·Hz1/2·W-1, a response time of 151 µs, and a polarization ratio of 2.83. The stable and rapid photoresponse of the device underpins the utility in infrared-coded communication and dual-channel imaging, showing the substantial potential of the detector. These findings articulate a systematic approach to developing miniaturized, multifunctional room-temperature infrared detectors with superior performance metrics and enhanced capabilities for multi-information acquisition.

Discovery and structural mechanism of DNA endonucleases guided by RAGATH-18-derived RNAs.

CRISPR-Cas systems and IS200/IS605 transposon-associated TnpBs have been utilized for the development of genome editing technologies. Using bioinformatics analysis and biochemical experiments, here we present a new family of RNA-guided DNA endonucleases. Our bioinformatics analysis initially identifies the stable co-occurrence of conserved RAGATH-18-derived RNAs (reRNAs) and their upstream IS607 TnpBs with an average length of 390 amino acids. IS607 TnpBs form programmable DNases through interaction with reRNAs. We discover the robust dsDNA interference activity of IS607 TnpB systems in bacteria and human cells. Further characterization of the Firmicutes bacteria IS607 TnpB system (ISFba1 TnpB) reveals that its dsDNA cleavage activity is remarkably sensitive to single mismatches between the guide and target sequences in human cells. Our findings demonstrate that a length of 20 nt in the guide sequence of reRNA achieves the highest DNA cleavage activity for ISFba1 TnpB. A cryo-EM structure of the ISFba1 TnpB effector protein bound by its cognate RAGATH-18 motif-containing reRNA and a dsDNA target reveals the mechanisms underlying reRNA recognition by ISFba1 TnpB, reRNA-guided dsDNA targeting, and the sensitivity of the ISFba1 TnpB system to base mismatches between the guide and target DNA. Collectively, this study identifies the IS607 TnpB family of compact and specific RNA-guided DNases with great potential for application in gene editing.

Glutathione safeguards TET-dependent DNA demethylation and is critical for the acquisition of totipotency and pluripotency during preimplantation development.

During early development, both genome-wide epigenetic reprogramming and metabolic remodeling are hallmark changes of normal embryogenesis. However, little is known about their relationship and developmental functions during the preimplantation window, which is essential for the acquisition of totipotency and pluripotency. Herein, we reported that glutathione (GSH), a ubiquitous intracellular protective antioxidant that maintains mitochondrial function and redox homeostasis, plays a critical role in safeguarding postfertilization DNA demethylation and is essential for establishing developmental potential in preimplantation embryos. By profiling mitochondria-related transcriptome that coupled with different pluripotency, we found GSH is a potential marker that is tightly correlated with full pluripotency, and its beneficial effect on prompting developmental potential was functionally conformed using in vitro fertilized mouse and bovine embryos as the model. Mechanistic study based on preimplantation embryos and embryonic stem cells further revealed that GSH prompts the acquisition of totipotency and pluripotency by facilitating ten-eleven-translocation (TET)-dependent DNA demethylation, and ascorbic acid (AsA)-GSH cycle is implicated in the process. In addition, we also reported that GSH serves as an oviductal paracrine factor that supports development potential of preimplantation embryos. Thus, our results not only advance the current knowledge of functional links between epigenetic reprogramming and metabolic remodeling during preimplantation development but also provided a promising approach for improving current in vitro culture system for assisted reproductive technology.

Deep Circumflex Iliac Artery-vascularized Iliac Bone Graft for Femoral Head Osteonecrosis: Computed Tomography Anatomical Study.

BACKGROUND: Deep circumflex iliac artery (DCIA)-vascularized iliac graft transposition is a method for treating femoral head osteonecrosis but with inconsistent efficacy. We aim to improve the method of this surgery by recommending the optimal location of the iliac pedicle to satisfy the vascular length for transposition and the blood supply of the vascularized iliac graft. METHODS: The DCIA and its surrounding tissues were assessed on computed tomography angiography images for 100 sides (left and right) of 50 patients. The length of the vascular pedicle required for transposition and the length of the pedicle at different iliac spine positions were compared. The diameter and cross-sectional area of the DCIA and the distance between the DCIA and iliac spine were measured at different points to assess blood supply. We also compared differences in sex and left-right position. RESULTS: The diameter and cross-sectional area of the DCIA gradually decreased after crossing the anterior superior iliac spine (ASIS), and it approached the iliac bone. However, when the DCIA was 4 cm behind the ASIS (54 sides, 54%), it coursed posteriorly and superiorly away from the iliac spine. The vascular length of the pedicle was insufficient to transpose the vascularized iliac graft to the desired position when it was within 1 cm of the ASIS. The vascular length requirement was satisfied, and the blood supply was sufficient when the pedicle was positioned at 2 or 3 cm. CONCLUSION: To obtain a satisfactory pedicle length and sufficient blood supply, the DCIA pedicle of the vascularized iliac graft should be placed 2 to 3 cm behind the ASIS. The dissection of DCIA has slight differences in sex and left-right position due to anatomical differences.

Enzyme Engineering Renders Chlorinase the Activity of Fluorinase.

Organofluorine compounds have attracted substantial attention owing to their wide application in agrochemistry. Fluorinase (FlA) is a unique enzyme in nature that can incorporate fluorine into an organic molecule. Chlorinase (SalL) has a similar mechanism as fluorinase and can use chloride but not fluoride as a substrate to generate 5'-chloro-deoxyadenosine (5'-ClDA) from S-adenosyl-l-methionine (SAM). Therefore, identifying the features that lead to this selectivity for halide ions is highly important. Here, we engineered SalL to gain the function of FlA. We found that residue Tyr70 plays a key role in this conversion through alanine scanning. Site-saturation mutagenesis experiments demonstrated that Y70A/C/S/T/G all exhibited obvious fluorinase activity. The G131S mutant of SalL, in which the previously thought crucial residue Ser158 for fluoride binding in FlA was introduced, did not exhibit fluorination activity. Compared with the Y70T single mutant, the double mutant Y70T/W129F increased 5'-fluoro-5-deoxyadenosine (5'-FDA) production by 76%. The quantum mechanics (QM)/molecular mechanics (MM) calculations suggested that the lower energy barriers and shorter nucleophilic distance from F- to SAM in the mutants than in the SalL wild-type may contribute to the activity. Therefore, our study not only renders SalL the activity of FlA but also sheds light on the enzyme selectivity between fluoride versus chloride.

Effect of acupuncture on regulating IL-17, TNF-ɑ and AQPs in Sjögren's syndrome.

AIM: The aim of the study was to observe the effect of acupuncture on regulating interleukin (IL)-17, tumor necrosis factor (TNF)-ɑ, and aquaporins (AQPs) in Sjögren's syndrome (SS) on patients and on non-obese diabetic (NOD) models. METHODS: Levels of anti-AQP 1, 5, 8, and 9 antibodies, IL-17, and TNF-ɑ in the serum of SS patients were compared prior and following 20 acupuncture treatment visits during 8 weeks. While in murine model, five groups were divided to receive interventions for 4 weeks, including control, model, acupuncture, isoflurane, and hydroxychloroquine. The submaxillofacial gland index, histology, immunohistochemistry of AQP1, 5, salivary flow, together with IL-17, and TNF-ɑ expression in peripheral blood were compared among the groups. RESULTS: Acupuncture reduced IL-17, TNF-ɑ, and immunoglobin A levels, and numeric analog scale of dryness in 14 patients with SS (p < 0.05). The salivary flow was increased, and the water intake decreased in NOD mice receiving acupuncture treatments. IL-17 and TNF-ɑ levels in peripheral serum were down-regulated (p < 0.05) and AQP1, 5 expression in the submandibular glands up-regulated in mice. CONCLUSION: The effect on relieving xerostomia with acupuncture may be achieved by up-regulating the expression of AQP1. AQP5, down-regulating levels of IL-17 and TNF-ɑ, and a decrease in inflammation of glands.

Integrated analysis of transcriptome and metabolome reveals the regulatory mechanism of largemouth bass (Micropterus salmoides) in response to Nocardia seriolae infection.

Nocardia seriolae is a severe bacterial pathogen that has seriously affected the development of aquaculture industry. Largemouth bass (Micropterus salmoides) is a commercially significant freshwater fish that suffers a variety of environmental threats, including bacterial pathogens. However, the immune responses and metabolic alterations of largemouth bass to N. seriolae infection remain largely unclear. We discovered that N. seriolae caused pathological alterations in largemouth bass and shifted the transcript of immune-related and apoptotic genes in head kidney after infection. To answer the aforementioned question, a combined transcriptome and metabolome analysis was employed to explore the alterations in genes, metabolites, and metabolic pathways in largemouth bass following bacterial infection. A total of 3579 genes and 1929 metabolites are significant differentially changed in the head kidney post infection. In response to N. seriolae infection, host modifies the PI3K-Akt signaling pathway, TCA cycle, glycolysis, and amino acid metabolism. The integrated analysis of transcriptome and metabolome suggested that with the arginine metabolism pathway as the core, multiple biomarkers (arg gene, arginine) are involved in the antibacterial and immune functions of largemouth bass. Thus, we hypothesized that arginine plays a crucial role in the immune responses of largemouth bass against N. seriolae infection, and increasing arginine levels suitably is beneficial for the host against bacterial infection. Our results shed light on the regulatory mechanism of largemouth bass resistance to N. seriolae infection and contributed to the development of more effective N. seriolae resistance strategies.

Effect of high-quality nursing on neurological function psychological moods quality of life of elderly patients with stroke.

Objectives: The primary objective of the present investigation was to meticulously examine the efficacy of high-quality nursing care (HQN) on neurological restoration, amelioration of adverse psychological states, and augmentation of quality of life in geriatric patients diagnosed with acute cerebral infarction (ACI). Methods: A cohort of 240 patients, afflicted by ACI and admitted to our healthcare institution between February 2020 and March 2023, were incorporated into this longitudinal prospective analysis. Employing a random number table methodology, the patient cohort was bifurcated into a control group (n = 120) receiving conventional care and an observation group (n = 120) receiving HQN. Comparisons were conducted between the two cohorts concerning neurological functionality [as quantified by the National Institutes of Health Stroke Scales (NIHSS) and Barthel Index (BI) scores], psychological wellbeing [utilizing the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores], overall quality of life [assessed via the Generic Quality of Life Inventory-74 (GQOLI-74) scores], and self-perceived burden [evaluated through the Self-Perceived Burden Scale (SPBS)]. Further assessments included patient satisfaction and incidence of complications, both in the pre- and post-interventional phases. Results: Post-intervention, the observation group demonstrated superior outcomes compared to the control group, as evidenced by diminished NIHSS and SPBS scores and elevated BI metrics. Moreover, SAS and SDS scores in both groups manifested a decline post-intervention; however, the decrement was statistically more pronounced in the observation group (P < 0.05). Similarly, all dimensions of GQOLI-74 showed an upward trend in both cohorts, yet the increase was significantly more substantial in the observation group (P < 0.05). Furthermore, the observation group exhibited a reduced frequency of complications coupled with heightened levels of nursing satisfaction. Conclusion: The implementation of HQN in the geriatric population afflicted by ACI markedly enhances neurological recuperation, attenuates adverse psychological states, and ameliorates overall quality of life. The intervention is also associated with a diminution in complication rates and an increase in nursing satisfaction, thereby substantiating its clinical utility.

A novel long-tailed myovirus represents a new T4-like cyanophage cluster.

Cyanophages affect the abundance, diversity, metabolism, and evolution of picocyanobacteria in marine ecosystems. Here we report an estuarine Synechococcus phage, S-CREM2, which represents a novel viral genus and leads to the establishment of a new T4-like cyanophage clade named cluster C. S-CREM2 possesses the longest tail (~418 nm) among isolated cyanomyoviruses and encodes six tail-related proteins that are exclusively homologous to those predicted in the cluster C cyanophages. Furthermore, S-CREM2 may carry three regulatory proteins in the virion, which may play a crucial role in optimizing the host intracellular environment for viral replication at the initial stage of infection. The cluster C cyanophages lack auxiliary metabolic genes (AMGs) that are commonly found in cyanophages of the T4-like clusters A and B and encode unique AMGs like an S-type phycobilin lyase gene. A variation in the composition of tRNA and cis-regulatory RNA genes was observed between the marine and freshwater phage strains in cluster C, reflecting their different modes of coping with hosts and habitats. The cluster C cyanophages are widespread in estuarine and coastal regions and exhibit equivalent or even higher relative abundance compared to those of clusters A and B cyanophages in certain estuarine regions. The isolation of cyanophage S-CREM2 provides new insights into the phage-host interactions mediated by both newly discovered AMGs and virion-associated proteins and emphasizes the ecological significance of cluster C cyanophages in estuarine environments.

Network pharmacology and in vivo studies reveal the neuroprotective effects of paeoniflorin on Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that has still not been effectively treated. Paeoniflorin is a traditional Chinese medicine with potential neuroprotective effects against brain injury; however, the beneficial effects and mechanisms of action in AD have not been clarified. We aimed to explore the mechanisms of action of paeoniflorin in AD using network pharmacology and experimental validation. Network pharmacology analysis revealed 30 candidate targets through the intersection of the targets of paeoniflorin and related genes in AD, which were mainly enriched in oxidative stress and inflammation. Moreover, key targets of paeoniflorin against AD, namely Nrf2 (encoded by NFE2L2) and TLR4, were screened and found to be closely related to oxidative stress and inflammation. Subsequent in vivo experiments revealed that paeoniflorin treatment improved the cognition of APP/PS1 mice by ameliorating oxidative stress and neuroinflammation, which were associated with the upregulation of Nrf2 and HO1, and the downregulation of TLR4. Collectively, the present study demonstrates that paeoniflorin alleviates cognitive impairment in AD by regulating oxidative stress and neuroinflammation, and that Nrf2, HO1, and TLR4 could be key targets.

Serum amyloid A is a potential predictor of prognosis in acute ischemic stroke patients after intravenous thrombolysis.

Objectives: Inflammation shows a notable relationship to acute ischemic stroke's (AIS) occurrence and prognosis. However, existing research has confirmed that serum amyloid A (SAA) is an inflammatory biomarker. The aim of this paper was to investigate the association between SAA and the three-month clinical results of acute AIS patients after intravenous thrombolysis (IVT). Methods: The evaluation of AIS patients with complete medical records was carried out by prospectively investigating patients hospitalized in our department between January 2020 and February 2023. The SAA levels were examined with the use of an immunosorbent assay kit that shows a relationship with the enzyme (Invitrogen Corp). Patients were dichotomized into favorable (mRS score of 0, 1 or 2) and unfavorable (mRS score of 3, 4, 5, or 6) results with the use of the modified Rankin Scale (mRS). Results: A total of 405 AIS patients who were subjected to IVT therapy were prospectively covered. To be specific, 121 (29.88%) patients had an unfavorable prognosis during the follow-up for 3 months. On that basis, patients achieving unfavorable results gained notably greater SAA levels (39.77 (IQR 38.32-46.23) vs.31.23 (IQR 27.44-34.47), p < 0.001) during hospitalization in comparison to patients with a better result. In the analysis with multiple variates, SAA was adopted to achieve the independent prediction of the three-month unfavorable clinical results of acute AIS patients after IVT [OR:2.874 (95% CI, 1.764-4.321), p < 0.001]. When the fundamental confounding factors were regulated, the odds ratio (OR) of unfavorable prognosis after AIS patients undergoing IVT therapy was 4.127 (95% CI = 1.695-10.464, p = 0.032) for the maximum tertile of SAA in terms of the minimal tertile. With an AUC of 0.703 (95% CI, 0.649-0.757), SAA revealed a notably more effective discriminating capability in terms of CRP, NLR, EMR, and WBC. SAA as a predictor in terms of the prediction of three-month unfavorable results after AIS patients undergoing IVT therapy achieved specificity and sensitivity of 84.45% and 77.23%, as well as an optimal cut-off value (COV) of 37.39. Conclusion: SAA level that is up-regulated during hospitalization is capable of serving as an effective marker in terms of the prediction of unfavorable three-month results in AIS patients after IVT.

Discovery of a cis-regulatory element SaeM involved in dynamic regulation of synergid-specific MYB98.

MYB98 is a key regulator of the genetic network behind pollen tube attraction toward the female gametophyte. MYB98 is specifically expressed in the synergid cells (SCs), a female gametophyte component cells specialized for pollen tube attraction. However, it had not been clear how exactly MYB98 achieves this specific expression pattern. In the current study, we have determined that a normal SC-specific expression of MYB98 is dependent on a 16-bp-long cis-regulatory element, CATTTACACATTAAAA, freshly named as the "S ynergid-specific A ctivation E lement of M YB98" (SaeM). An 84 bp fragment harboring SaeM in the middle was sufficient to drive exclusively SC-specific expression. The element was present in a significantly large proportion of SC-specific gene promoters and in the promoter of MYB98 homologous genes in the Brassicaceae (pMYB98s). Significance of such family-wide SaeM-like element conservation in exclusive SC-specific expression was confirmed by the Arabidopsis-like activation feature of Brassica oleracea-derived pMYB98 and absence of such feature of pMYB98 derived from a non-Brassicaceae member Prunus persica. Additionally, the yeast-one-hybrid assay showed that the SaeM can be recognized by ANTHOCYANINLESS2 (ANL2) and DAP-seq data further suggested for additional three ANL2 homologs targeting the similar cis-element. Overall, our study has concluded that SaeM plays a crucial role in driving exclusively SC-specific expression of MYB98 and strongly suggests for the involvement of ANL2 and its homologs in its dynamic regulation in planta. Future study on the transcription factors is expected to shed more light on the mechanism behind the process.

Hierarchical S-Scheme Heterostructure of CdIn2S4@UiO-66-NH2 toward Synchronously Boosting Photocatalytic Removal of Cr(VI) and Tetracycline.

Developing highly efficient photocatalysts toward synchronously removing heavy metals and organic pollutants is still a serious challenge. Herein, we depict hierarchical S-scheme heterostructured photocatalysts prepared via in situ anchoring UiO-66-NH2 nanoparticles onto the CdIn2S4 porous microsphere structures assembled with numerous nanosheets. In the mixed system of Cr(VI) and tetracycline (TC), the optimal photocatalyst (CIS@U66N-30) shows remarkable photocatalytic activities toward the synchronous removal of Cr(VI) (97.26%) and TC (close to 100% of) under visible-light irradiation for 60 min, being the best removal rates among those of the reported photocatalysts, and sustains the outstanding stability and reusability. Its reaction rate constants of Cr(VI) reduction and TC degradation are about 2.06 and 1.58 folds that in the single Cr(VI) and TC systems, respectively. The enhanced photocatalytic activities of CIS@U66N-30 mainly result from the following synergism: (1) its hierarchical structure offers abundant active sites, and the S-scheme migration mechanism of charge carriers in the heterostructure accelerates the separation and migration of the useful photoinduced electrons and holes with the high redox capability; (2) Cr(VI) and TC can serve as the electron scavenger for TC oxidation degradation and the hole and •OH scavenger for Cr(VI) reduction, respectively, further enhancing the separation and utilization efficiency of photoinduced electrons and holes. Besides, the possible TC degradation pathway and plausible S-scheme photocatalytic mechanism over CIS@U66N-30 for the concurrent elimination of Cr(VI) and TC are proposed.