ARTseq-FISH reveals position-dependent differences in gene expression of micropatterned mESCs.

Differences in gene-expression profiles between individual cells can give rise to distinct cell fate decisions. Yet how localisation on a micropattern impacts initial changes in mRNA, protein, and phosphoprotein abundance remains unclear. To identify the effect of cellular position on gene expression, we developed a scalable antibody and mRNA targeting sequential fluorescence in situ hybridisation (ARTseq-FISH) method capable of simultaneously profiling mRNAs, proteins, and phosphoproteins in single cells. We studied 67 (phospho-)protein and mRNA targets in individual mouse embryonic stem cells (mESCs) cultured on circular micropatterns. ARTseq-FISH reveals relative changes in both abundance and localisation of mRNAs and (phospho-)proteins during the first 48 hours of exit from pluripotency. We confirm these changes by conventional immunofluorescence and time-lapse microscopy. Chemical labelling, immunofluorescence, and single-cell time-lapse microscopy further show that cells closer to the edge of the micropattern exhibit increased proliferation compared to cells at the centre. Together these data suggest that while gene expression is still highly heterogeneous position-dependent differences in mRNA and protein levels emerge as early as 12 hours after LIF withdrawal.

Competition mode and soil nutrient status shape the role of soil microbes in the diversity-invasibility relationship.

Understanding the relationship between plant diversity and invasibility is essential in invasion ecology. Species-rich communities are hypothesized to be more resistant to invasions than species-poor communities. However, while soil microorganisms play a crucial role in regulating this diversity-invasibility relationship, the effects of plant competition mode and soil nutrient status on their role remain unclear. To address this, we conducted a two-stage greenhouse experiment. Soils were first conditioned by growing nine native species separately in them for 1 year, then mixed in various configurations with soils conditioned using one, three, or six species, respectively. Next, we inoculated the mixed soil into sterilized substrate soil and planted the alien species Rhus typhina and native species Ailanthus altissima as test plants. We set up two competition modes (intraspecific and interspecific) and two nutrient levels (fertilization using slow-release fertilizer and nonfertilization). Under intraspecific competition, regardless of fertilization, the biomass of the alien species was higher in soil conditioned by six native species. By contrast, under interspecific competition, the biomass increased without fertilization but remained stable with fertilization in soil conditioned by six native species. Analysis of soil microbes suggests that pathogens and symbiotic fungi in diverse plant communities influenced R. typhina growth, which varied with competition mode and nutrient status. Our findings suggest that the soil microbiome is pivotal in mediating the diversity-invasibility relationship, and this influence varies according to competition mode and nutrient status.

Dual-Energy-Barrier Stable Superhydrophobic Structures for Long Icing Delay.

Using superhydrophobic surfaces (SHSs) with the water-repellent Cassie-Baxter (CB) state is widely acknowledged as an effective approach for anti-icing performances. Nonetheless, the CB state is susceptible to diverse physical phenomena (e.g., vapor condensation, gas contraction, etc.) at low temperatures, resulting in the transition to the sticky Wenzel state and the loss of anti-icing capabilities. SHSs with various micronanostructures have been empirically examined for enhancing the CB stability; however, the energy barrier transits from the metastable CB state to the stable Wenzel state and thus the CB stability enhancement is currently not enough to guarantee a well and appliable anti-icing performance at low temperatures. Here, we proposed a dual-energy-barrier design strategy on superhydrophobic micronanostructures. Rather than the typical single energy barrier of the conventional CB-to-Wenzel transition, we introduced two CB states (i.e., CB I and CB II), where the state transition needed to go through CB I and CB II then to Wenzel state, thus significantly improving the entire CB stability. We applied ultrafast laser to fabricate this dual-energy-barrier micronanostructures, established a theoretical framework, and performed a series of experiments. The anti-icing performances were exhibited with long delay icing times (over 27,000 s) and low ice-adhesion strengths (0.9 kPa). The kinetic mechanism underpinning the enhanced CB anti-icing stability was elucidated and attributed to the preferential liquid pinning in the shallow closed structures, enabling the higher CB-Wenzel transition energy barrier to sustain the CB state. Comprehensive durability tests further corroborated the potentials of the designed dual-energy-barrier structures for anti-icing applications.

Antiviral therapy response in patients with chronic hepatitis B and fatty liver: A systematic review and meta-analysis.

The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to systematically review and analyse antiviral treatment response in CHB patients with and without FL. We searched PubMed, Embase, Web of Science and the Cochrane Library databases from inception to 31 May 2023 for relevant studies. Biochemical response (BR), complete viral suppression (CVS) and hepatitis B e antigen (HBeAg) seroconversion in CHB patients with FL (CHB-FL) and without FL (non-FL CHB) were compared. In an initial pool of 2101 citations, a total of 10 studies involving 2108 patients were included. After 12 weeks of treatment, CHB-FL patients as compared with non-FL CHB patients had lower BR rate (48.37% [108/227] vs. 72.98% [126/174], p = .04) but similar trend for CVS (36.86% [80/227] vs. 68.81% [114/174], p = .05) and similar rates of HBeAg seroconversion (6.59% [7/103] vs. 7.40% [7/110], p = .89). However, at week 48, there were no statistically significant differences between CHB-FL and non-FL CHB patients in any of the outcomes, including BR (60.03% [213/471] vs. 69.37% [314/717], p = .67), CVS (65.63% [459/746] vs. 73.81% [743/1132], p = .27) and HBeAg seroconversion (10.01% [30/275] vs. 14.06% [65/453], p = .58) with similar findings for week 96. BR rate was lower in CHB-FL patients after 12 weeks of antiviral treatment. However, after a longer follow-up of either 48 or 96 weeks, no statistically significant differences were observed in BR, CVS or HBeAg seroconversion rates between CHB patients with and without FL.

Thermally stable Ni foam-supported inverse CeAlOx/Ni ensemble as an active structured catalyst for CO2 hydrogenation to methane.

Nickel is the most widely used inexpensive active metal center of the heterogeneous catalysts for CO2 hydrogenation to methane. However, Ni-based catalysts suffer from severe deactivation in CO2 methanation reaction due to the irreversible sintering and coke deposition caused by the inevitable localized hotspots generated during the vigorously exothermic reaction. Herein, we demonstrate the inverse CeAlOx/Ni composite constructed on the Ni-foam structure support realizes remarkable CO2 methanation catalytic activity and stability in a wide operation temperature range from 240 to 600 °C. Significantly, CeAlOx/Ni/Ni-foam catalyst maintains its initial activity after seven drastic heating-cooling cycles from RT to 240 to 600 °C. Meanwhile, the structure catalyst also shows water resistance and long-term stability under reaction condition. The promising thermal stability and water-resistance of CeAlOx/Ni/Ni-foam originate from the excellent heat and mass transport efficiency which eliminates local hotspots and the formation of Ni-foam stabilized CeAlOx/Ni inverse composites which effectively anchored the active species and prevents carbon deposition from CH4 decomposition.

Oerskovia flava sp. nov., a deoxynivalenol (DON)-degrading actinomycete isolated from the rhizosphere soil of long-term continuous cropping cucumber.

The deoxynivalenol (DON)-degrading bacterium JB1-3-2 T was isolated from a rhizosphere soil sample of cucumber collected from a greenhouse located in Zhenjiang, Eastern China. The JB1-3-2 T strain is a Gram-stain-positive, nonmotile and round actinomycete. Growth was observed at temperatures between 15 and 40 ℃ (optimum, 35 ℃), in the presence of 15% (w/v) NaCl (optimum, 3%), and at pH 3 and 11 (optimum, 7). The major cellular fatty acids identified were anteiso-C15:0, iso-C16:0 and anteiso-C17:0. Genome sequencing revealed a genome size of 4.11 Mb and a DNA G + C content of 72.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the JB1-3-2 T strain was most closely related to type strains of the Oerskovia species, with the highest sequence similarity to Oerskovia turbata NRRL B-8019 T (98.2%), and shared 98.1% sequence identity with other valid type strains of this genus. Digital DNA‒DNA hybridization (dDDH) and average nucleotide identity (ANI) showed 21.8-22.2% and 77.2-77.3% relatedness, respectively, between JB1-3-2 T and type strains of the genus Oerskovia. Based on genotypic, phylogenetic, chemotaxonomic, physiological and biochemical characterization, Oerskovia flava, a novel species in the genus Oerskovia, was proposed, and the type strain was JB1-3-2 T (= CGMCC 1.18555 T = JCM 35248 T). Additionally, this novel strain has a DON degradation ability that other species in the genus Oerskovia do not possess, and glutathione-S-transferase was speculated to be the key enzyme for strain JB1-3-2 T to degrade DON.

Tumor-associated macrophage subtypes on cancer immunity along with prognostic analysis and SPP1-mediated interactions between tumor cells and macrophages.

Tumor-associated macrophages (TAM) subtypes have been shown to impact cancer prognosis and resistance to immunotherapy. However, there is still a lack of systematic investigation into their molecular characteristics and clinical relevance in different cancer types. Single-cell RNA sequencing data from three different tumor types were used to cluster and type macrophages. Functional analysis and communication of TAM subpopulations were performed by Gene Ontology-Biological Process and CellChat respectively. Differential expression of characteristic genes in subpopulations was calculated using zscore as well as edgeR and Wilcoxon rank sum tests, and subsequently gene enrichment analysis of characteristic genes and anti-PD-1 resistance was performed by the REACTOME database. We revealed the heterogeneity of TAM, and identified eleven subtypes and their impact on prognosis. These subtypes expressed different molecular functions respectively, such as being involved in T cell activation, apoptosis and differentiation, or regulating viral bioprocesses or responses to viruses. The SPP1 pathway was identified as a critical mediator of communication between TAM subpopulations, as well as between TAM and epithelial cells. Macrophages with high expression of SPP1 resulted in poorer survival. By in vitro study, we showed SPP1 mediated the interactions between TAM clusters and between TAM and tumor cells. SPP1 promoted the tumor-promoting ability of TAM, and increased PDL1 expression and stemness of tumor cells. Inhibition of SPP1 attenuated N-cadherin and ß-catenin expression and the activation of AKT and STAT3 pathway in tumor cells. Additionally, we found that several subpopulations could decrease the sensitivity of anti-PD-1 therapy in melanoma. SPP1 signal was a critical pathway of communication between macrophage subtypes. Some specific macrophage subtypes were associated with immunotherapy resistance and prognosis in some cancer types.

Naphthalene Diimide-Based Metallacage as an Artificial Ion Channel for Chloride Ion Transport.

Developing synthetic molecular devices for controlling ion transmembrane transport is a promising research field in supramolecular chemistry. These artificial ion channels provide models to study ion channel diseases and have huge potential for therapeutic applications. Compared with self-assembled ion channels constructed by intermolecular weak interactions between smaller molecules or cyclic compounds, metallacage-based ion channels have well-defined structures and can exist as single components in the phospholipid bilayer. A naphthalene diimide-based artificial chloride ion channel is constructed through efficient subcomponent self-assembly and its selective ion transport activity in large unilamellar vesicles and the planar lipid bilayer membrane by fluorescence and ion-current measurements is investigated. Molecular dynamics simulations and density functional theory calculations show that the metallacage spans the entire phospholipid bilayer as an unimolecular ion transport channel. This channel transports chloride ions across the cell membrane, which disturbs the ion balance of cancer cells and inhibits the growth of cancer cells at low concentrations.

Design of intelligent inspection system for solder paste printing defects based on improved YOLOX.

Aiming at the current SPI (solder paste inspection) system for printing solder paste similar defects detection accuracy is not high, the system intelligence degree is low and so on, design a for the solder paste similar defects and combined with phase modulation profile measurement technique and improve the YOLOX intelligent detection system. The core of the system is the improved YOLOX depth model based on s-mosica and kt-iou algorithms proposed in this paper. The experimental results show that the proposed s-mosica and kt-iou algorithms can effectively improve the detection accuracy of printed solder paste, and when combined with the YOLOX model, the best 90.33% detection accuracy is obtained, which is better than the detection performance of the existing algorithms in the same scenario, and it provides an effective and feasible reference program for the design of the SPI high-precision intelligent detection system.

Efficacy and Safety of Botulinum Toxin Type A in the Treatment of Trigeminal Neuralgia: An Update on Systematic Review With Meta-analyses.

OBJECTIVE: Pain management in patients with TN is challenging, as facial pain often does not respond well to conventional therapies. Botulinum toxin type A (BTX-A) has been suggested as a potential treatment option, but there is limited evidence regarding its long-term efficacy. This review aimed to analyze the current data for the use of in the treatment of trigeminal neuralgia (TN) and highlight the evidence for its efficacy and safety. METHODS: A comprehensive search was conducted in various databases (PubMed, Scopus, Embase, ClinicalTrials, and Cochrane Library) to identify clinical studies evaluating the use of BTX-A in TN until October 2023. Randomized controlled trials (RCTs), single-arm studies, and stratified studies were included in the analysis. The mean difference (MD), effect size (ES), and 95% confidence interval (CI) were estimated for visual analogue scale (VAS) scores, pain episode frequency, and the proportion of responders. RESULTS: The analysis included 23 studies, including 4 RCTs, 14 single-arm studies, and 5 stratified studies. In the RCTs, BTX-A was found to significantly reduce mean VAS scores compared with baseline (ES: -4.05; 95% CI: -6.13, -1.97; P =0.002). In 19 non-RCTs, the pooled single-arm analysis revealed that BTX-A decreased VAS scores (ES: -5.19, 95% CI: -6.05, -4.33, P <0.001) and pain attack frequency (ES: -17.85, 95% CI: -23.36, -12.34, P <0.001) from baseline to the end of follow-up. The overall proportion of responders to BTX-A treatment was also significant (95% CI: 0.653, 0.761, P =0.003). DISCUSSION: Current evidence indicates that BTX-A injection is an effective and safe option for patients with refractory TN or not responding to medical or surgical management. However, more high-quality studies are needed to further confirm its efficacy.

Multi-Functional Spirobifluorene Phosphonate Based Exciplex Interface Enables Voc Reaching 95% of Theoretical Limit for Perovskite Solar Cells.

Metal halide perovskite solar cells (PSCs) show significant advancements in power conversion efficiency (PCE). However, the open-circuit voltage (VOC) of PSCs is limited by interfacial factors such as defect-induced recombination, energy band mismatch, and non-intimate interface contact. Here, an exciplex interface is first developed based on the strategically designed and synthesized two spirobifluorene phosphonate molecules to mitigate VOC loss in PSCs. The exciplex interface constructed by the intimate contact between the multi-functional molecules and hole transport layer takes the roles to promote the hole extraction by donor-acceptor interaction, passivate coordination-unsaturated Pb2+ defects by equipped phosphonate groups, and optimize the energy level alignment. As a result, a record VOC of 1.26 V with a perovskite bandgap of 1.61 eV is achieved, representing over 95% of theoretical limit. This advancement leads to an increase in PCE from 21.29% to 24.12% and improved stability. The exciplex interface paves the way for addressing the long-standing challenge of VOC loss and promotes the wider application of PSCs.

Exploration of the utility of different doses of Qingfei Dayuan granules: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Clinical studies have confirmed that Qingfei Dayuan (QFDY) granules are effective in the treatment of influenza and upper respiratory tract infections (URTIs) caused by pulmonary heat-toxin syndrome (PHTS). Granules of Chinese medicine formulations have become a widely used dosage form in clinical practice. With the continuous optimization of extraction technology, the advantages of Chinese medicine granules have been gradually demonstrated, but the price of Chinese medicine granules is generally higher than that of traditional dosage forms of Chinese medicine, and we support the rational use of the appropriate dosage of QFDY for patients with these conditions. Therefore, we set up half of the conventional dose as the low dose group, and designed the three-arm study to rigorously compare the efficacy difference of low-dose QFDY, QFDY and the placebo group, with the expectation of providing scientific support for the rational selection of the dose and the safe and effective use of the medicine in clinical practice. METHODS: We recruited 108 patients with clinical diagnoses of influenza and URTIs caused by PHTS to receive treatment at six hospitals in Hubei, China. Using a centralized randomization system, patients were randomly assigned at a 1:1:1 ratio to the QFDY, low-dose QFDY, or placebo control groups to receive the corresponding drug, and the study physicians, subjects, outcome assessors, and statisticians were unaware of group assignments. The primary outcome was the time to complete fever relief. Secondary outcomes included the efficacy of Chinese medicine in alleviating signs and symptoms and the disappearance rate of individual symptoms. Adverse events were monitored throughout the trial. RESULTS: A total of 108 patients were recruited. A total of 106 patients were included in the full analysis set (FAS). In the FAS analysis, there was no statistically significant difference in baseline of the three groups before treatment (P > 0.05). 1. Regarding the median time to complete fever relief, the QFDY, low-dose QFDY and placebo groups had median times of 26 h, 40 h and 48 h, respectively. The QFDY group had a shorter time to complete fever relief than the placebo group, and the difference was statistically significant (P < 0.05), while the low-dose QFDY group had a shorter time than the placebo group, but the difference was not statistically significant (P > 0.05). 2. In terms of the total efficacy of Chinese medicine in alleviating symptoms at the end of three full days of treatment, as well as the cure rate of red and sore throat, stuffy and runny nose, and sneezing, QFDY and low-dose QFDY were superior to the placebo, and the differences were statistically significant (P < 0.01). There was no statistical significance in the comparison between the QFDY group and the low-dose QFDY group (P > 0.05). 3. In terms of the headache cure rate after three full days of treatment, QFDY was superior to the placebo, with a statistically significant difference (P < 0.05), and there was no significant efficacy of low-dose QFDY. 4. Safety comparisons showed no serious adverse events and 30 minor adverse events, which were not clinically considered to be related to the drug and were not statistically significant. CONCLUSIONS: In the treatment of patients with influenza and URTIs caused by PHTS, which are mainly characterized by clinical symptoms such as red and sore throat, stuffy and runny nose, and sneezing, when fever is not obvious or low-grade fever is present, the use of low-dose QFDY to simply alleviate the clinical symptoms is recommended and preferred. Moreover, with its good safety profile, QFDY can be used in the treatment of patients with influenza and URTIs caused by PHTS, which can effectively shorten the duration of fever, significantly increase the total efficacy of Chinese medicine in alleviating symptoms after 3 days of treatment, and accelerate the recovery of symptoms such as red and sore throat, stuffy and runny nose, sneezing, and headache, etc. Clinical Trial Registration: http://www.chictr.org.cn. TRIAL NUMBER: ChiCTR2100043449. Registered on 18 February 2021.

Aluminum ion chemistry of Na4Fe3(PO4)2(P2O7) for all-climate full Na-ion battery.

Na4Fe3(PO4)2(P2O7) (NFPP) is currently drawing increased attention as a sodium-ion batteries (SIBs) cathode due to the cost-effective and NASICON-type structure features. Owing to the sluggish electron and Na+ conductivities, however, its real implementation is impeded by the grievous capacity decay and inferior rate capability. Herein, multivalent cation substituted microporous Na3.9Fe2.9Al0.1(PO4)2(P2O7) (NFAPP) with wide operation-temperature is elaborately designed through regulating structure/interface coupled electron/ion transport. Greatly, the derived Na vacancy and charge rearrangement induced by trivalent Al3+ substitution lower the ions diffusion barriers, thereby endowing faster electron transport and Na+ mobility. More importantly, the existing Al-O-P bonds strengthen the local environment and alleviate the volume vibration during (de)sodiation, enabling highly reversible valence variation and structural evolution. As a result, remarkable cyclability (over 10,000 loops), ultrafast rate capability (200 C), and exceptional all-climate stability (-40-60 °C) in half/full cells are demonstrated. Given this, the rational work might provide an actionable strategy to promote the electrochemical property of NFPP, thus unveiling the great application prospect of sodium iron mixed phosphate materials.

Effect of acidosis on adipose-derived stem cell impairment and gene expression.

Based on disappointing results of stem cell-based application in clinical trials for patients with critical limb ischemia, we hypothesized that the acidic environment might be the key factor limiting cell survival and function. In the present study, we used microdialysis to determine presence of acidosis and metabolic imbalance in critical ischemia. Moreover, we explored the effect of extracellular acidosis on adipose-derived stem cells (ADSCs) at molecular and transcriptional level. Our data demonstrate that low pH negatively regulates cell proliferation and survival, also, it results in cell cycle arrest, mitochondrial dynamics disorder, DNA damage as well as the impairment of proangiogenic function in a pH-dependent manner. Further transcriptome profiling identified the pivotal signaling pathways and hub genes in response to acidosis. Collectively, these findings provide strong evidences for a critical role of acidosis in ADSCs impairment with ischemic condition and suggest treatments focus on tissue pH balance and acidosis-mediated hub genes may have therapeutic potential in stem cell-based application.

Changes of the volatile compounds and odors in one-stage and three-stage infant formulas during their secondary shelf-life.

The odor of infant formula changes due to alterations in its volatile composition during the shelf life. However, there is currently a lack of research on whether the odor changes in infant formula during the secondary shelf life, which refers to the period of repeated opening and usage in daily life. This study used headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-electrostatic orbitrap high-resolution mass spectrometry (GC-Orbitrap-MS) to investigate the volatile composition changes in one-stage and three-stage infant formulas during different stages (0 day, 3 days, and 7 days during the secondary shelf-life, i.e. simulated daily use). A total of 32 volatiles were identified, including nine aldehydes, seven ketones, four alcohols, three furans, two sulfur compounds, two esters, and five terpenoids. Of these, 16 compounds changed significantly in one-stage samples and 23 compounds in three-stage samples within 7 days of the secondary shelf-life. Further the odor of the three-stage infant formula samples was found changed substantially after 3 days of simulated use by using the triangle test. This study highlighted the considerable alterations in volatile compound composition and sensory changes during the simulated daily use and provided valuable insights for consumers in selecting and using infant formula products, as well as a new perspective for enterprises to improve the sensory quality of their products.

Preparation of a novel cadmium-containing coordination polymer and catalytic application in the synthesis of N-alkylated aminoquinoline derivatives via the borrowing hydrogen approach.

Herein, we report an efficient and straightforward approach for the synthesis of N-alkylated aminoquinoline derivatives by recyclable Cd-containing coordination polymer-catalyzed reactions of aminoquinolines with primary alcohols via the borrowing hydrogen strategy. In this work, a new type of coordination polymer [Cd(CIA)(phen)2(H2O)]n was successfully designed and fabricated. The molecular structure was corroborated by single-crystal X-ray diffraction and fully characterized by PXRD, FT-IR, TGA, and XPS. Importantly, this polymer revealed high catalytic activity for the N-alkylation reaction of 2-aminoquinoline and 8-aminoquinoline with inexpensive and low-toxicity alcohols as alkylating agents in excellent yields up to 95%. Interestingly, the present synthetic protocol was successfully applied for the gram-level synthesis of several biologically active compounds. In addition, several control reactions were carried out to investigate the possible mechanisms of this transformation. Finally, recycling experiments indicated that the cadmium coordination polymer showed good recovery performance for borrowing hydrogen reactions.

Different minimal alcohol consumption in male and female individuals with metabolic dysfunction-associated fatty liver disease.

BACKGROUND AND AIMS: The relationship between moderate alcohol intake and health outcomes among individuals with metabolic dysfunction-associated fatty liver disease (MAFLD) is complex. Our aim was to investigate the association of minimal alcohol consumption with all-cause and cause-specific mortality among MAFLD individuals of different genders. METHODS: Our study included 2630 MAFLD individuals from the Third National Health and Nutrition Examination Survey. Cox regression analysis was performed to assess the association between alcohol use measures and all-cause and cause-specific mortality. Restricted cubic spline curves were used to evaluate the relationship between alcohol consumption per week and all-cause mortality. RESULTS: In the entire MAFLD cohort, we observed significant disparities in clinical characteristics between male and female individuals with MAFLD. Higher weekly alcohol consumption was significantly associated with all-cause and cause-specific mortality (male, hazard ratios [HRs]: 1.009, 95% CIs: 1.004-1.014; female, HRs: 1.032, 95% CIs: 1.022-1.042). In males with MAFLD, a linear association with all-cause mortality was observed for weekly alcohol consumption (p for non-linearity = .21). Conversely, in females with MAFLD, the risk of all-cause mortality remained relatively stable until 2 drinks per week, after which it rapidly increased with each additional drink consumed, and the increase in mortality risk was higher than that observed in males (p for non-linearity < .05). CONCLUSIONS: Our findings indicate that any increase in weekly alcohol consumption was associated with increased all-cause mortality in men with MAFLD. Conversely, consuming less than 2 drinks per week had minimal impact on the risk of mortality among female.

Nocardioides limicola sp. nov., an alkaliphilic alkane degrading bacterium isolated from oilfield alkali-saline soil.

A Gram-stain-positive, rod-shaped, non-spore-forming, alkane degrading bacterium, designated DJM-14T, was isolated from oilfield alkali-saline soil in Heilongjiang, Northeast China. On the basis of 16 S rRNA gene sequencing, strain DJM-14T was shown to belong to the genus Nocardioides, and related most closely to Nocardioides terrigena KCTC 19,217T (95.53% 16 S rRNA gene sequence similarity). Strain DJM-14T was observed to grow at 25-35 °C, pH 7.0-11.0, in the presence of 0-6.0% (w/v) NaCl. The predominant respiratory quinone was MK-8 (H4) and LL-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The major fatty acids were identified as iso-C16:0 and C18:1 ω9c. It contained diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol as the polar lipids. The genome (3,722,608 bp), composed of 24 contigs, had a G + C content of 69.6 mol%. Out of the 3667 predicted genes, 3618 were protein-coding genes, and 49 were ncRNAs. Digital DNA-DNA hybridization (dDDH) estimation and average nucleotide identity (ANI) of strain DJM-14T against genomes of the type strains of related species in the same family ranged between 18.7% and 20.0%; 68.8% and 73.6%, respectively. According to phenotypic, genotypic and phylogenetic data, strain DJM-14T represents a novel species in the genus Nocardioides, for which the name Nocardioides limicola sp. nov. is proposed and the type strain is DJM-14T (= CGMCC 4.7593T, =JCM 33,692T). In addition, novel strains were able to grow with n-alkane (C24-C36) as the sole carbon source. Multiple copies of alkane 1-monooxygenase (alkB) gene, as well as alcohol dehydrogenase gene and aldehyde dehydrogenase gene involved in the alkane assimilation were annotated in the genome of type strain DJM-14T.

DNA Gate-Based CRISPR-Cas Exponential Amplification System for Ultrasensitive Small Extracellular Vesicle Detection to Enhance Breast Cancer Diagnosis.

Tumor-derived small extracellular vesicles (tEVs) as potential biomarkers possess abundant surface proteins closely related to parent cells, which are crucial for noninvasive cancer diagnosis. However, tEVs exhibit phenotype heterogeneity and low abundance, posing a significant challenge for multiplex detection with a high sensitivity. Herein, we developed a DNA gate-based exponential amplification CRISPR-Cas (DGEAC) system for accurate and ultrasensitive detection of tEVs, which can greatly improve the accuracy of breast cancer (BC) diagnosis. Based on the coexpression of CD63 and vascular endothelial growth factor (VEGF) on BC-derived tEVs, we developed a dual-aptamer-based AND gate fluorescent probe by proximity hybridization. By integrating the target recognition and trans-cleavage activity of Cas12a, an autocatalysis-driven exponential amplification circuit was developed for ultrasensitive detection of CD63 and VEGF proteins on tEVs, which could avoid false negative signals from single protein or other interfering proteins. We achieved highly sensitive detection of tEVs over a linear range from 1.75 × 103 to 3.5 × 108 particles/mL with a detection limit as low as 1.02 × 103 particles/mL. Furthermore, the DGEAC system can distinguish tEVs from tEVs derived from different BC cell lines, including MDA-MB-231, MCF-7, SKBR3, and MCF-10A. Compared to linear amplification (AUC 90.0%), the DGEAC system effectively differentiates BC in different stages (AUC 98.3%).

The Emerging Role of Deubiquitinases in Radiosensitivity.

Radiation therapy is a primary treatment for cancer, but radioresistance remains a significant challenge in improving efficacy and reducing toxicity. Accumulating evidence suggests that deubiquitinases (DUBs) play a crucial role in regulating cell sensitivity to ionizing radiation. Traditional small-molecule DUB inhibitors have demonstrated radiosensitization effects, and novel deubiquitinase-targeting chimeras (DUBTACs) provide a promising strategy for radiosensitizer development by harnessing the ubiquitin-proteasome system. This review highlights the mechanisms by which DUBs regulate radiosensitivity, including DNA damage repair, the cell cycle, cell death, and hypoxia. Progress on DUB inhibitors and DUBTACs is summarized, and their potential radiosensitization effects are discussed. Developing drugs targeting DUBs appears to be a promising alternative approach to overcoming radioresistance, warranting further research into their mechanisms.