High-Fidelity Spatiotemporal Recognition of Golgi ALP through an Initial-Accumulation and Postactivation Strategy.

Various signal molecules mediate complex physiological processes collectively in the Golgi. However, most currently accessible probes are questionable in illuminating the functions of these reactive species in Golgi because of the inability to irradiate these probes only at the desired Golgi location, which compromises specificity and accuracy. In this study, we rationally designed the first photocontrollable and Golgi-targeted fluorescent probe to in situ visualize the Golgi alkaline phosphatase (ALP). The designed probe with natural yellow fluorescence can provide access into Golgi and monitor the exact timing of accumulation in Golgi. On-demand photoactivation at only the desired Golgi location affords a significant emission response to ALP with illuminating red fluorescence at 710 nm. Through the photocontrollable fluorescence responsiveness to ALP, precise spatiotemporal recognition of Golgi ALP fluctuations is successfully performed. With this probe, for the first time, we revealed the Golgi ALP levels during cisplatin-induced acute kidney injury (AKI), which will further facilitate and complement the comprehensive exploration of ALP kinetics during physiological and pathological processes.

Homology and heterogeneity of soil trace elements of coal power production bases in arid and semi-arid areas of Northwest China.

Coal power activities could cause regional fluctuations of trace elements, but the distribution information of these trace elements in arid and semi-arid areas is insufficient. In this study, the soil trace elements (As, B, Be, Cd, Co, Cr, Cu, Fe, Ga, Ge, Mn, Mo, Ni, Pb, Sb, Sn, Sr, Ti, Tl, and Zn) of Ningdong Coal Power Production Base in China were monitored. Results showed that the concentrations of B, Tl, Mn, Pb, Cr, K, Cu, and Co exceeded background values. The maximum risk index reached 265.66, while the trace elements posed a cancer risk to children. Combining correlation analyses (CA), principal component analysis (PCA), and positive matrix factorization (PMF) techniques, it indicated that trace elements were mainly coming from coal combustion (34.15%), livestock farming (17.44%), traffic emissions (12.42%), and natural factors (35.99%). This study reveals the sources and potential ecological risks of soil trace elements in the Ningdong Coal and Power Production Base. It provides a scientific basis for developing targeted environmental management measures and reducing human health risks.

In vitro inhibitory effects of selumetinib on activity of human UDP-glucuronosyltransferases and prediction of in vivo drug-drug interactions.

Selumetinib is an oral, effective, and selective tyrosine kinase inhibitor targeting mitogen-activated protein kinase 1 and 2 (MEK1/2), which is clinically active in multiple tumor types, such as neurofibromatosis type 1 (NF1), melanoma, gliomas and non-small cell lung cancer (NSCLC). The purpose of this article was to assess the effects of selumetinib on the activities of twelve human UDP-glucosyltransferases (UGTs) including UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15, and 2B17, and its potential for inducing clinical drug-drug interactions (DDIs). The results demonstrated that selumetinib potently inhibited the activity of UGT2B7 through the mechanism of mixed inhibition with the inhibition constant value of 5.79 ± 0.65 µM. Furthermore, the plasma concentration of UGT2B7 substrate as the co-administered drug was predicted to be increased by at least 84 % when patients took selumetinib 75 mg twice daily, suggesting a high potential to induce clinical DDIs. Selumetinib exhibited weak inhibitory effects on other human UGTs and was unlikely to trigger off UGTs-mediated DDIs except for UGT2B7. Therefore, the combination of selumetinib with the substrate drug of UGT2B7 requires additional attention to avoid adverse events in clinical treatment.

Global trends in the research on older population dizziness/vertigo: a 20-year bibliometric and visualization analysis.

OBJECTIVE: Dizziness or vertigo in older population frequently presents in clinical settings, yet its etiology remains elusive. The objective of this study was to delineate global trends and identify frontiers in research concerning dizziness or vertigo among older population. METHODS: We searched the research literature published from 2003 to 2022 on older population with dizziness or vertigo using two databases from the Web of Science Core Collection. A bibliometric and visualization analysis was conducted. Bibliometric tools facilitated co-authorship, co-citation, and keyword co-occurrence analyses, encompassing countries or regions, institutions, authors, journals, and references. RESULTS: The analysis included 1322 publications authored by 6524 individuals from 2244 institutions across 67 countries or regions, spanning 92 subject categories. A steady increase in publications was noted from 2003 to 2022. The University of Munich, Harvard University, and the University of California System emerged as leading institutions with the highest publication outputs. The United States, Germany, and China were predominant in publication counts. Eva Grill was identified as the most prolific author. Otology & Neurotology and Geriatrics & Gerontology emerged as the most prolific journal and subject category, respectively. The most prevalent keywords were "dizziness", "vertigo", "falls", and "geriatric", with "management", "gait", and "association" recognized as the principal research hotspots. CONCLUSION: This study provides a systematic analysis of global scientific research on older population dizziness/vertigo, revealing significant advancements in understanding over the past two decades. Management, gait, and association have emerged as the primary research focuses on recent years. These findings offer valuable insights for directing current research efforts to capture prevailing trends and explore new frontiers in this field.

Local hydrogen bonding environment induces the deprotonation of surface hydroxyl for continuing ammonia decomposition.

There is still a paucity of fundamental understanding about the reaction of ammonia decomposition over TiO2, especially the role of water. Herein, FPMD and DFT calculations were used to address this concern. The results reveal that ammonia decomposition in pure ammonia causes the hydroxylation of the surfaces and reduction of the proton acceptor sites, making proton transfer (PT) difficult, increasing the distances between the NH3 and Obr sites and changing the adsorption configurations of NH3, which are not favourable for accepting protons from NH3 dissociation. When water is introduced, the local hydrogen bonding environment, consisting of NH3 and H2O with the H2O dynamically close to the ObrH, promotes the increase of the positive charge of H atoms from 0.133 to 1.47 e, which increases the ObrH bond dipole moment from 1.136 to 1.400 Debye, resulting in the shortening of the H-bond distances between NH3 and ObrH (1.858 vs. 1.945 Å of only NH3) and enlarging the ObrH bonds (0.980 vs. 1.120 Å). This reduces the activation energy barriers of ObrH deprotonation and causes the surfaces to have low hydroxyl coverage from 0.425 to 0.382 eV. Our study reveals the role of water and provides new insights into ammonia decomposition on TiO2.

Assessment of urine sample collection and processing variables for extracellular vesicle-based proteomics.

Extracellular vesicles (EVs) in urine are a promising source for developing non-invasive biomarkers. However, urine concentration and content are highly variable and dynamic, and actual urine collection and handling often is nonideal. Furthermore, patients such as those with prostate diseases have challenges in sample collection due to difficulties in holding urine at designated time points. Here, we simulated the actual situation of clinical sample collection to examine the stability of EVs in urine under different circumstances, including urine collection time and temporary storage temperature, as well as daily urine sampling under different diet conditions. EVs were isolated using functionalized EVtrap magnetic beads and characterized by nanoparticle tracking analysis (NTA), western blotting, electron microscopy, and mass spectrometry (MS). EVs in urine remained relatively stable during temporary storage for 6 hours at room temperature and for 12 hours at 4 °C, while significant fluctuations were observed in EV amounts from urine samples collected at different time points from the same individuals, especially under certain diets. Sample normalization with creatinine reduced the coefficient of variation (CV) values among EV samples from 17% to approximately 6% and facilitated downstream MS analyses. Finally, based on the results, we applied them to evaluate potential biomarker panels in prostate cancer by data-independent acquisition (DIA) MS, presenting the recommendation that can facilitate biomarker discovery with nonideal handling conditions.

Characterization and correlations of dominant microorganisms and volatile compounds in fermentation process of Yangjiang douchi.

BACKGROUND: Yangjiang douchi (YD) is a traditional fermented soybean product, which is popular in Chinese cuisine for its unique flavor. However, due to its high salt content and unstable flavor, its competitiveness in the international market is gradually weakening. Microorganisms have a key role in the production process of YD because it is a fermented food but the effect of microorganisms on the volatile compounds of YD is also not currently clear. RESULTS: In this paper, aroma compounds and microbial diversity in different fermentation stages of YD were analyzed using gas chromatography-mass spectrometry/olfactometry (GC-MS/O) and IlluminaMiseq system sequencing. A total of 78 aroma-active compounds were detected throughout the fermentation process and they influenced the formation of flavor in YD. Fungi flora were relatively single in YD, and bacteria were rich and varied. A total of 418 species of bacteria were present during fermentation, with unclassified_Staphylococcus, Staphylococcus_kloosii, and Bacillus_velezensis_Bacillus predominating. There were 25 species of fungi at the species level, and Aspergillus minisclerotigenes (OTU 4) played a dominant role in the whole fermentation process. CONCLUSION: Staphylococcus and Bacillus in the bacterial genus were strongly correlated with most flavor compounds detected, and A. minisclerotigenes in the fungi were more relevant to flavor compounds. This research provides a theoretical basis for the enhancement of the flavor of traditional fermented douchi in China. © 2024 Society of Chemical Industry.

Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection.

The treatment of severe acute pancreatitis (SAP), with high mortality rates, poses a significant clinical challenge. Investigating the pathological changes associated with SAP using animal models can aid in identifying potential therapeutic targets and exploring novel treatment approaches. Previous studies primarily induced pancreatic injury through retrograde bile duct injection of sodium taviaurocholate, but the impact of surgical damage on the quality of the animal model remains unclear. In this study, we employed various frequencies of intraperitoneal Caerulein injections combined with different doses of LPS to induce pancreatic injury in C57BL/6J mice and compared the extent of injury across five intraperitoneal injection protocols. Regarding inducing acute pancreatitis in mice, an intraperitoneal injection protocol is proposed that results in a mortality rate as high as 80% within 5 days. Specifically, mice received ten daily intraperitoneal injections of Caerulein (50 µg/kg), followed by an injection of LPS (15 mg/kg) one hour after the last Caerulein administration. By adjusting the frequency and dosage of injected medications, one can manipulate the severity of pancreatic injury effectively. This model exhibits strong controllability and has a short replication cycle, making it feasible for completion by a single researcher without requiring expensive equipment. It conveniently and accurately simulates key disease characteristics observed in human SAP while demonstrating a high degree of reproducibility.

High Safety Electrolyte Design for Enabling High Energy-Density System of LiNi0.8Co0.1Mn0.1O2//Phosphorus by Simultaneously Adjusting Dual Electrode/Electrolyte Interfaces.

The demand for state-of-the-art high-energy-density lithium-ion batteries is increasing. However, the low specific capacity of electrode materials in conventional full-cell systems cannot meet the requirements. Ni-rich layered oxide cathodes such as Li(Ni0.8Co0.1Mn0.1)O2 (NCM811) have a high theoretical specific capacity of 200 mAh g-1, but it is always accompanied by side reactions on the electrode/electrolyte interface. Phosphorus anode possesses a high theoretical specific capacity of 2596 mAh g-1, but it has a huge volume expansion (≈300%). Herein, a highly compatible and secure electrolyte is reported via introducing an additive with a narrow electrochemical window, Lithium difluoro(oxalato)borate (LiDFOB), into 1 m LiPF6 EC/DMC with tris (2,2,2-trifluoroethyl) phosphate (TFEP) as a cosolvent. LiDFOB participates in the formation of organic/inorganic hybrid electrode/electrolyte interface layers at both the cathode and anode sides. The side reactions on the surface of the NCM811 cathode and the volume expansion of the phosphorus anode are effectively alleviated. The NCM811//RP full cell in this electrolyte shows high capacity retention of 82% after 150 cycles at a 0.5C rate. Meanwhile, the electrolyte shows non-flammability. This work highlights the importance of manipulating the electrode/electrolyte interface layers for the design of lithium-ion batteries with high energy density.

Effects of Respiratory Function Exercise and Psychological Nursing on COPD Patients: A Comprehensive Study.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a prevalent and impactful respiratory condition, necessitating effective interventions for improved patient outcomes. This retrospective analysis aimed to explore the efficacy of respiratory function exercise combined with psychological nursing on cardiopulmonary function index, exercise tolerance, and quality of life in patients with stable COPD. Methods: The data of 100 patients with stable COPD admitted to Cangzhou Central Hospital from June 2019 to June 2021 were retrospectively analyzed. Patients were assigned to the experimental group (n=50) and the control group (n=50) alphabetically by their initials. Patients in both groups were treated with conventional care combined with respiratory function exercise, and the experimental group additionally received psychological care intervention. Pulmonary function indicators, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), one-second rate (FEV1/FVC), 6-min walking test (6MWT) results, quality of life (physical health and role emotional), anxiety and depression self-rating scale scores, nursing satisfaction, and clinical efficacy were compared between the two groups before and after treatment. Results: The two groups presented no significant differences in baseline data (P > .05). The experimental group outperformed the control group in terms of pulmonary function index, quality of life, and nursing satisfaction (P < .001). The observation group obtained lower negative emotion scores than the control group after nursing intervention (P < .001). After nursing, the FEV1/FVC in the experimental group was significantly higher than that in the control group [(58.63 ± 5.64) vs (46.36 ± 5.23)]. The 6MWT results in the experimental group were significantly better than those in the control group [(398.35 ± 28.65) m vs (348.97 ± 26.98) m] (all P < .001). Conclusion: The results revealed that this combined approach effectively improves lung function, mitigates negative emotions, enhances nursing satisfaction, and significantly boosts the quality of life in patients with stable COPD. These findings underscore the potential clinical relevance of implementing such interventions for better COPD management and patient well-being.

Phase separation-competent FBL promotes early pre-rRNA processing and translation in acute myeloid leukaemia.

RNA-binding proteins (RBPs) are pivotal in acute myeloid leukaemia (AML), a lethal disease. Although specific phase separation-competent RBPs are recognized in AML, the effect of their condensate formation on AML leukaemogenesis, and the therapeutic potential of inhibition of phase separation are underexplored. In our in vivo CRISPR RBP screen, fibrillarin (FBL) emerges as a crucial nucleolar protein that regulates AML cell survival, primarily through its phase separation domains rather than methyltransferase or acetylation domains. These phase separation domains, with specific features, coordinately drive nucleoli formation and early processing of pre-rRNA (including efflux, cleavage and methylation), eventually enhancing the translation of oncogenes such as MYC. Targeting the phase separation capability of FBL with CGX-635 leads to elimination of AML cells, suggesting an additional mechanism of action for CGX-635 that complements its established therapeutic effects. We highlight the potential of PS modulation of critical proteins as a possible therapeutic strategy for AML.

The relative contribution of PM2.5 components to the obstructive ventilatory dysfunction-insights from a large ventilatory function examination of 305,022 workers in southern China.

BACKGROUND: The new round of WHO/ILO Joint Estimates of the Work-related Burden of Disease assessment requires futher research to provide more evidence, especially on the health impact of ambient air pollution around the workplace. However, the evidence linking obstructive ventilatory dysfunction (OVD) to fine particulate matter (PM2.5) and its chemical components in workers is very limited. Evidence is even more scarce on the interactive effects between occupational factors and particle exposures. We aimed to fill these gaps based on a large ventilatory function examination of workers in southern China. METHODS: We conducted a cross-sectional study among 363,788 workers in southern China in 2020. The annual average concentration of PM2.5 and its components were evaluated around the workplace through validated spatiotemporal models. We used mixed-effect models to evaluate the risk of OVD related to PM2.5 and its components. Results were further stratified by basic characteristics and occupational factors. FINDINGS: Among the 305,022 workers, 119,936 were observed with OVD. We found for each interquartile range (IQR) increase in PM2.5 concentration, the risk of OVD increased by 27.8 (95 % confidence interval (CI): 26.5-29.2 %). The estimates were 10.9 % (95 %CI: 9.7-12.1 %), 15.8 % (95 %CI: 14.5-17.2 %), 2.6 % (95 %CI: 1.4-3.8 %), 17.1 % (95 %CI: 15.9-18.4 %), and 11 % (95 %CI: 9.9-12.2 %), respectively, for each IQR increment in sulfate, nitrate, ammonium salt, organic matter and black carbon. We observed greater effect estimates among females, younger workers, workers with a length of service of 24-45 months, and professional skill workers. Furthermore, it is particularly noteworthy that the noise-exposed workers, high-temperature-exposed workers, and less-dust-exposed workers were at a 5.7-68.2 % greater risk than others. INTERPRETATION: PM2.5 and its components were significantly associated with an increased risk of OVD, with stronger links among certain vulnerable subgroups.

POSoligo software for in vitro gene synthesis.

Oligonucleotide synthesis is vital for molecular experiments. Bioinformatics has been employed to create various algorithmic tools for the in vitro synthesis of nucleotides. The main approach to synthesizing long-chain DNA molecules involves linking short-chain oligonucleotides through ligase chain reaction (LCR) and polymerase chain reaction (PCR). Short-chain DNA molecules have low mutation rates, while LCR requires complementary interfaces at both ends of the two nucleic acid molecules or may alter the conformation of the nucleotide chain, leading to termination of amplification. Therefore, molecular melting temperature, length, and specificity must be considered during experimental design. POSoligo is a specialized offline tool for nucleotide fragment synthesis. It optimizes the oligonucleotide length and specificity based on input single-stranded DNA, producing multiple contiguous long strands (COS) and short patch strands (POS) with complementary ends. This process ensures free 5'- and 3'-ends during oligonucleotide synthesis, preventing secondary structure formation and ensuring specific binding between COS and POS without relying on stabilizing the complementary strands based on Tm values. POSoligo was used to synthesize the linear RBD sequence of SARS-CoV-2 using only one DNA strand, several POSs for LCR ligation, and two pairs of primers for PCR amplification in a time- and cost-effective manner.

Fast-Charging Phosphorus-Based Anodes: Promises, Challenges, and Pathways for Improvement.

Fast-charging batteries are highly sought after. However, the current battery industry has used carbon as the preferred anode, which can suffer from dendrite formation problems at high current density, causing failure after prolonged cycling and posing safety hazards. The phosphorus (P) anode is being considered as a promising successor to graphite due to its safe lithiation potential, low ion diffusion energy barrier, and high theoretical storage capacity. Since 2019, fast-charging P-based anodes have realized the goals of extreme fast charging (XFC), which enables a 10 min recharging time to deliver a capacity retention larger than 80%. Rechargeable battery technologies that use P-based anodes, along with high-capacity conversion-type cathodes or high-voltage insertion-type cathodes, have thus garnered substantial attention from both the academic and industry communities. In spite of this activity, there remains a rather sparse range of high-performance and fast-charging P-based cell configurations. Herein, we first systematically examine four challenges for fast-charging P-based anodes, including the volumetric variation during the cycling process, the electrode interfacial instability, the dissolution of polyphosphides, and the long-lasting P/electrolyte side reactions. Next, we summarize a range of strategies with the potential to circumvent these challenges and rationally control electrochemical reaction processes at the P anode. We also consider both binders and electrode structures. We also propose other remaining issues and corresponding strategies for the improvement and understanding of the fast-charging P anode. Finally, we review and discuss the existing full cell configurations based on P anodes and forecast the potential feasibility of recycling spent P-based full cells according to the trajectory of recent developments in batteries. We hope this review affords a fresh perspective on P science and engineering toward fast-charging energy storage devices.

The OGT-c-Myc-PDK2 axis rewires the TCA cycle and promotes colorectal tumor growth.

Deregulated glucose metabolism termed the "Warburg effect" is a fundamental feature of cancers, including the colorectal cancer. This is typically characterized with an increased rate of glycolysis, and a concomitant reduced rate of the tricarboxylic acid (TCA) cycle metabolism as compared to the normal cells. How the TCA cycle is manipulated in cancer cells remains unknown. Here, we show that O-linked N-acetylglucosamine (O-GlcNAc) regulates the TCA cycle in colorectal cancer cells. Depletion of OGT, the sole transferase of O-GlcNAc, significantly increases the TCA cycle metabolism in colorectal cancer cells. Mechanistically, OGT-catalyzed O-GlcNAc modification of c-Myc at serine 415 (S415) increases c-Myc stability, which transcriptionally upregulates the expression of pyruvate dehydrogenase kinase 2 (PDK2). PDK2 phosphorylates pyruvate dehydrogenase (PDH) to inhibit the activity of mitochondrial pyruvate dehydrogenase complex, which reduces mitochondrial pyruvate metabolism, suppresses reactive oxygen species production, and promotes xenograft tumor growth. Furthermore, c-Myc S415 glycosylation levels positively correlate with PDK2 expression levels in clinical colorectal tumor tissues. This study highlights the OGT-c-Myc-PDK2 axis as a key mechanism linking oncoprotein activation with deregulated glucose metabolism in colorectal cancer.

A regulation strategy of self-assembly molecules for achieving efficient inverted perovskite solar cells.

Self-assembled monolayers (SAMs) have been successfully employed to enhance the efficiency of inverted perovskite solar cells (PSCs) and perovskite/silicon tandem solar cells due to their facile low-temperature processing and superior device performance. Nevertheless, depositing uniform and dense SAMs with high surface coverage on metal oxide substrates remains a critical challenge. In this work, we propose a holistic strategy to construct composite hole transport layers (HTLs) by co-adsorbing mixed SAMs (MeO-2PACz and 2PACz) onto the surface of the H2O2-modified NiOx layer. The results demonstrate that the conductivity of the NiOx bulk phase is enhanced due to the H2O2 modification, thereby facilitating carrier transport. Furthermore, the hydroxyl-rich NiOx surface promotes uniform and dense adsorption of mixed SAM molecules while enhancing their anchoring stability. In addition, the energy level alignment at the interface is improved due to the utilization of mixed SAMs in an optimized ratio. Furthermore, the perovskite film crystal growth is facilitated by the uniform and dense composite HTLs. As a result, the power conversion efficiency of PSCs based on composite HTLs is boosted from 22.26% to 23.16%, along with enhanced operational stability. This work highlights the importance of designing and constructing NiOx/SAM composite HTLs as an effective strategy for enhancing both the performance and stability of inverted PSCs.