Rapid Targeted Screening and Identification of Active Ingredients in Herbal Extracts through Ligand-Detected NMR and Database Matching.

Herbal extracts are rich sources of active compounds that can be used for drug screening due to their diverse and unique chemical structures. However, traditional methods for screening these compounds are notably laborious and time-consuming. In this manuscript, we introduce a new high-throughput approach that combines nuclear magnetic resonance (NMR) spectroscopy with a tailored database and algorithm to rapidly identify bioactive components in herbal extracts. This method distinguishes characteristic signals and structural motifs of active constituents in the raw extracts through a relaxation-weighted technique, particularly utilizing the perfect echo Carr-Purcell-Meiboom-Gill (peCPMG) sequence, complemented by precise 2D spectroscopic strategies. The cornerstone of our approach is a customized database designed to filter potential compounds based on defined parameters, such as the presence of CHn segments and unique chemical shifts, thereby expediting the identification of promising compounds. This innovative technique was applied to identifying substances interacting with choline kinase α (ChoKα1), resulting in the discovery of four new inhibitors. Our findings demonstrate a powerful tool for unraveling the complex chemical landscape of herbal extracts, considerably facilitating the search for new pharmaceutical candidates. This approach offers an efficient alternative to traditional methods in the quest for drug discovery from natural sources.

Management considerations and treatment outcomes for newly diagnosed prostate cancer in advanced age patients (≥80 years): real-world data from a single urological center over a 10-year period.

Background: There is ongoing debate regarding prostate cancer (PCa) screening in advanced age males, leading to treatment decisions often based on tumor staging and life expectancy. A critical gap in clinical evidence and tailored guidelines for the advanced age with PCa persists. This study aims to compare survival outcomes of various treatment approaches in this demographic. Methods: We analyzed data from a large urological center for advanced age patients suspected of having PCa between 2012 and 2022. We collected clinical and pathological characteristics and evaluated treatment modalities, including palliative therapy and definitive therapy. Propensity score matching (PSM) analysis was implemented to reduce bias between treatment modalities. Kaplan-Meier and multivariate Cox proportional hazard regression analyses were conducted to evaluate progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: Out of 4,333 suspected patients, 376 individuals aged 80 years and older underwent prostate biopsy. The overall detection rate of PCa was 78.7%, with a high prevalence of high-grade tumors [International Society of Urological Pathology (ISUP) grade ≥2]. Most patients (86.5%) received palliative therapy, while 13.5% underwent definitive therapy. Patients in the definitive therapy group had lower prostate-specific antigen (PSA) values, lower tumor stage, and Charlson Comorbidity Index (CCI), longer life expectancy, and a higher Geriatric 8 (G8) score compared to the palliative therapy group. The median OS for the entire cohort was 72.0 months, with 70.0 months for palliative therapy and 96.0 months for definitive therapy. Multivariable analyses identified lymphatic and bone metastasis, as well as definitive therapy, as independent prognostic factors for PFS, CSS, and OS. Conclusions: Advanced age patients, although a small group, have distinct characteristics, including higher PSA levels, positive biopsy rates, and pathological grading and staging. In medically fit elderly patients, especially those with localized PCa and a life expectancy of ≥5 years, definitive therapy could improve survival outcomes.

Lysine methylation: A strategy to improve in-cell NMR spectroscopy of proteins.

BACKGROUND: In-cell NMR is a valuable technique for investigating protein structure and function in cellular environments. However, challenges arise due to highly crowded cellular environment, where nonspecific interactions between the target protein and other cellular components can lead to signals broadening or disappearance in NMR spectra. RESULTS: We implemented chemical reduction methylation to selectively modify lysine residues on protein surfaces aiming to weaken charge interactions and recover obscured NMR signals. This method was tested on six proteins varying in molecular size and lysine content. While methylation did not disrupt the protein's native conformation, it successful restored some previously obscured in-cell NMR signals, particularly for proteins with high isoelectric points that decreased post-methylation. SIGNIFICANCE: This study affirms lysine methylation as a feasible approach to enhance the sensitivity of in-cell NMR spectra for protein studies. By mitigating signal loss due to nonspecific interactions, this method expands the utility of in-cell NMR for investigating proteins in their natural cellular environment, potentially leading to more accurate structural and functional insights.

S-Methyl-L-cysteine targeting MsrA attenuates Ang II-induced oxidative stress and atrial remodeling via the p38 MAPK signaling pathway.

Atrial fibrillation (AF) is the most prevalent sustained tachyarrhythmia in patients with cardiovascular diseases. Recently, it has been discovered that oxidative stress is an important contributor to AF. Therefore, antioxidant therapies for AF have great potential for clinical applications. Methionine, a sulfur-containing amino acid residue other than cysteine, is recognized as a functional redox switch, which could be rescued from the reversible oxidation of methionine sulfoxide by methionine sulfoxide reductase A (MsrA). S-Methyl-L-cysteine (SMLC), a natural analogue of Met, which is abundantly found in garlic and cabbage, could substitute for Met oxidations and mediate MsrA to scavenge free radicals. However, whether SMLC alleviates AF is unclear. This study aims to clarify the effects of SMLC on AF and elucidate the underlying pharmacological and molecular mechanisms. In vivo, SMLC (70, 140 and 280 mg kg-1 day-1) was orally administered to mice for 4 weeks with angiotensin II (Ang II) by subcutaneous infusion using osmotic pumps to induce AF. Ang II significantly prompted high AF susceptibility and atrial remodeling characterized by oxidative stress, conductive dysfunction and fibrosis. SMLC played a remarkable protective role in Ang II-induced atrial remodeling dose-dependently. Moreover, RNA sequencing was performed on atrial tissues to identify the differentially expressed mRNA, which was to screen out MSRA, CAMK2 and MAPK signaling pathways. Western blots confirmed that Ang II-induced downregulation of MsrA and upregulation of oxidized CaMKII (ox-CaMKII) and p38 MAPK could be reversed in a concentration-dependent manner by SMLC. To investigate the underlying mechanisms, HL-1 cells (mouse atria-derived cardiomyocytes) treated with Ang II were used for an in vitro model. SMLC alleviated Ang II-induced cytotoxicity, mitochondrial damage and oxidative stress. Additionally, knockdown MsrA could attenuate the protective effects of SMLC, which were eliminated by the p38 MAPK inhibitor SB203580. In summary, the present study demonstrates that SMLC protects against atrial remodeling in AF by inhibiting oxidative stress through the mediation of the MsrA/p38 MAPK signaling pathway.

Theory and application of robust linear phase-shift algorithm for phase-shift deflectometry method.

Based on the polynomial theory, the error propagation characteristics of the widely used N-step discrete Fourier transform (N-DFT) phase-shift algorithm were analyzed via theoretical analysis, under the effect of Gamma distortion and phase detuning. The results showed that the N-DFT algorithm could not simultaneously suppress both types of error. A robust linear phase-shift (RLPS) algorithm was designed, the performance of the RLPS and 8-DFT algorithms in terms of spectral response, detuning robustness, and G S / N was briefly analysis by Manuel Servin method. The Simulation analysis and comparison of the results show that the RLPS algorithm could suppress both types of error simultaneously, which exhibited better stability and accuracy than N-DFT and exponential algorithms, particularly in gradient measurement stability, peak-to-valley (PV) and root-mean-square (RMS) error suppression. Moreover, a physical experiment apparatus was built to test unidirectionally inclined plane mirror and concave mirror using the RLPS, N-DFT, and exponential algorithms. The results showed that the RLPS algorithm could significantly improve the measurement stability and accuracy in the presence of detuning and without screen Gamma calibration.

Temperature-driven shifts in bacterioplankton biodiversity: Implications for cold-preferred species in warming Tibetan proglacial lakes.

Recent climate warming and associated glacier retreat have dramatically changed the environmental conditions and microbial inhabitants of proglacial lakes. However, our understanding of the effects of climate warming and glacial influence on microbial biodiversity in these lakes remain relatively limited. Here, we studied bacterioplankton communities in 22 proglacial lakes on the Tibetan Plateau, spanning a range of nearly 7 °C in mean annual temperature (MAT), and examined the effects of climate and glaciers on their biodiversity by a space-to-time substitution. MAT emerged as the primary environmental driver of bacterioplankton biodiversity compared to glacial influence, increasing species richness and decreasing ß-diversity. We identified 576 low-MAT (cold-preferred) species and 2,088 high-MAT (warm-preferred) species, and found that low-MAT species are less environmentally adapted, with their numbers declining as temperature increased. These results advance our understanding of temperature-driven bacterioplankton dynamics by disentangling the contrasting responses and adaptations of cold-preferred and warm-preferred species. Our findings highlight the vulnerability of cold-specialist taxa and the potential biodiversity losses associated with climate warming in the rapidly changing proglacial lakes.

Dynorphin modulates motivation through a pallido-amygdala cholinergic circuit.

The endogenous opioid peptide dynorphin and its receptor κ-opioid receptor (KOR) have been implicated in divergent behaviors, but the underlying mechanisms remain elusive. Here we show that dynorphin released from nucleus accumbens dynorphinergic neurons exerts powerful modulation over a ventral pallidum (VP) disinhibitory circuit, thereby controlling cholinergic transmission to the amygdala and motivational drive in mice. On one hand, dynorphin acts postsynaptically via KORs on local GABAergic neurons in the VP to promote disinhibition of cholinergic neurons, which release acetylcholine into the amygdala to invigorate reward-seeking behaviors. On the other hand, dynorphin also acts presynaptically via KORs on dynorphinergic terminals to limit its own release. Such autoinhibition keeps cholinergic neurons from prolonged activation and release of acetylcholine, and prevents perseverant reward seeking. Our study reveals how dynorphin exquisitely modulate motivation through cholinergic system, and provides an explanation for why these neuromodulators are involved in motivational disorders, including depression and addiction.

Glycosylation of 2-(2-Propylsulfinyl)benzyl 1,2-Orthoester Glycosides Initiated by Sulfoxide Activation.

We have developed a highly effective glycosylation method that involves the activation of 2-(2-propylsulfinyl)benzyl 1,2-orthoester glycosides using triflic anhydride (Tf2O). Our research indicates that half of the glycosyl donor is activated through Tf2O via an interrupted Pummerer reaction mechanism, while the remaining portion is activated by triflic acid (TfOH) generated in situ. As a result, as little as 0.5 equiv of Tf2O is adequate for activating the orthoester glycoside donors. This glycosylation procedure offers several benefits, such as high efficiency, wide applicability, and the utilization of a recyclable leaving group.

[Hypothetical Alcohol Consumption Interventions and Hepatic Steatosis: A Longitudinal Study in a Large Cohort]. / æ¨¡æ‹Ÿé¥®é ’å¹²é¢„ä¸Žè‚è„‚è‚ªå˜æ€§ï¼šä¸€é¡¹å¤§åž‹é˜Ÿåˆ—çš„çºµå‘ç ”ç©¶.

Objective: Non-alcoholic fatty liver disease (NAFLD) and alcohol-associated fatty liver disease (ALD) are the most common chronic liver diseases. Hepatic steatosis is an early histological subtype of both NAFLD and ALD. Excessive alcohol consumption is widely known to lead to hepatic steatosis and subsequent liver damage. However, reported findings concerning the association between moderate alcohol consumption and hepatic steatosis remain inconsistent. Notably, alcohol consumption as a modifiable lifestyle behavior is likely to change over time, but most previous studies covered alcohol intake only once at baseline. These inconsistent findings from existing studies do not inform decision-making concerning policies and clinical guidelines, which are of greater interest to health policymakers and clinician-scientists. Additionally, recommendations on the types of alcoholic beverages are not available. Usually, assessing the effects of two or more hypothetical alcohol consumption interventions on hepatic steatosis provides answers to questions concerning the population risk of hepatic steatosis if everyone changes from heavy drinking to abstinence, or if everyone keeps on drinking moderately, or if everyone of the drinking population switches from red wine to beer? Thus, we simulated a target trial to estimate the effects of several hypothetical interventions, including changes in the amount of alcohol consumption or the types of alcoholic beverages consumed, on hepatic steatosis using longitudinal data, to inform decisions about alcohol-related policymaking and clinical care. Methods: This longitudinal study included 12687 participants from the UK Biobank (UKB), all of whom participated in both baseline and repeat surveys. We excluded participants with missing data related to components of alcohol consumption and fatty liver index (FLI) in the baseline and the repeat surveys, as well as those who had reported liver diseases or cancer at the baseline survey. We used FLI as an outcome indicator and divided the participants into non-, moderate, and heavy drinkers. The surrogate marker FLI has been endorsed by many international organizations' guidelines, such as the European Association for the Study of the Liver. The calculation of FLI was based on laboratory and anthropometric data, including triglyceride, gamma-glutamyl transferase, body mass index, and waist circumference. Participants responded to questions about the types of alcoholic beverages, which were defined in 5 categories, including red wine, white wine/fortified wine/champagne, beer or cider, spirits, and mixed liqueurs, along with the average weekly or monthly amounts of alcohol consumed. Alcohol consumption was defined as pure alcohol consumed per week and was calculated according to the amount of alcoholic beverages consumed per week and the average ethanol content by volume in each alcoholic beverage. Participants were categorized as non-drinkers, moderate drinkers, and heavy drinkers according to the amount of their alcohol consumption. Moderate drinking was defined as consuming no more than 210 g of alcohol per week for men and 140 g of alcohol per week for women. We defined the following hypothetical interventions for the amount of alcohol consumed: sustaining a certain level of alcohol consumption from baseline to the repeat survey (e.g., none to none, moderate to moderate, heavy to heavy) and changing from one alcohol consumption level to another (e.g., none to moderate, moderate to heavy). The hypothetical interventions for the types of alcoholic beverages were defined in a similar way to those for the amount of alcohol consumed (e.g., red wine to red wine, red wine to beer/cider). We applied the parametric g-formula to estimate the effect of each hypothetical alcohol consumption intervention on the FLI. To implement the parametric g-formula, we first modeled the probability of time-varying confounders and FLI conditional on covariates. We then used these conditional probabilities to estimate the FLI value if the alcohol consumption level of each participant was under a specific hypothetical intervention. The confidence interval was obtained by 200 bootstrap samples. Results: For the alcohol consumption from baseline to the repeat surveys, 6.65% of the participants were sustained non-drinkers, 63.68% were sustained moderate drinkers, and 14.74% were sustained heavy drinkers, while 8.39% changed from heavy drinking to moderate drinking. Regarding the types of alcoholic beverages from baseline to the repeat surveys, 27.06% of the drinkers sustained their intake of red wine. Whatever the baseline alcohol consumption level, the hypothetical interventions for increasing alcohol consumption from the baseline alcohol consumption were associated with a higher FLI than that of the sustained baseline alcohol consumption level. When comparing sustained non-drinking with the hypothetical intervention of changing from non-drinking to moderate drinking, the mean ratio of FLI was 1.027 (95% confidence interval [CI]: 0.997-1.057). When comparing sustained non-drinking with the hypothetical intervention of changing from non-drinking to heavy drinking, the mean ratio of FLI was 1.075 (95% CI: 1.042-1.108). When comparing sustained heavy drinking with the hypothetical intervention of changing from heavy drinking to moderate drinking, the mean ratio of FLI was 0.953 (95% CI: 0.938-0.968). The hypothetical intervention of changing to red wine in the UKB was associated with lower FLI levels, compared with sustained consumption of other types of alcoholic beverages. For example, when comparing sustaining spirits with the hypothetical intervention of changing from spirits to red wine, the mean ratio of FLI was 0.981 (95% CI: 0.948-1.014). Conclusions: Regardless of the current level of alcohol consumption, interventions that increase alcohol consumption could raise the risk of hepatic steatosis in Western populations. The findings of this study could inform the formulation of future practice guidelines and health policies. If quitting drinking is challenging, red wine may be a better option than other types of alcoholic beverages in Western populations.

Lifestyle factors and their relative contributions to longitudinal progression of cardio-renal-metabolic multimorbidity: a prospective cohort study.

BACKGROUND: The role of lifestyle factors and their relative contributions to the development and mortality of cardio-renal-metabolic multimorbidity (CRMM) remains unclear. METHODS: A study was conducted with 357,554 UK Biobank participants. CRMM was defined as the coexistence of two or three cardio-renal-metabolic diseases (CRMDs), including cardiovascular disease (CVD), type 2 diabetes (T2D) and chronic kidney disease (CKD). The prospective study examined the associations of individual and combined lifestyle scores (diet, alcohol consumption, smoking, physical activity, sedentary behavior, sleep duration and social connection) with longitudinal progression from healthy to first cardio-renal-metabolic disease (FCRMD), then to CRMM, and ultimately to death, using a multistate model. Subsequently, quantile G-computation was employed to assess the relative contribution of each lifestyle factor. RESULTS: During a median follow-up of 13.62 years, lifestyle played crucial role in all transitions from healthy to FCRMD, then to CRMM, and ultimately to death. The hazard ratios (95% CIs) per score increase were 0.91 (0.90, 0.91) and 0.90 (0.89, 0.91) for healthy to FCRMD, and for FCRMD to CRMM, and 0.84 (0.83, 0.86), 0.87 (0.86, 0.89), and 0.90 (0.88, 0.93) for mortality risk from healthy, FCRMD, and CRMM, respectively. Among the seven factors, smoking status contributed to high proportions for the whole disease progression, accounting for 19.88-38.10%. High-risk diet contributed the largest proportion to the risk of transition from FCRMD to CRMM, with 22.53%. Less-frequent social connection contributed the largest proportion to the risk of transition from FCRMD to death, with 28.81%. When we further consider the disease-specific transitions, we find that lifestyle scores had slightly stronger associations with development to T2D than to CVD or CKD. CONCLUSIONS: Our study indicates that a healthy lifestyle may have a protective effect throughout the longitudinal progression of CRMM, informing more effective management and treatment. Smoking status, diet, and social connection played pivotal roles in specific disease transitions.

Temporal relationship between hepatic steatosis and fasting blood glucose elevation: a longitudinal analysis from China and UK.

BACKGROUND: The link between nonalcoholic fatty liver disease and type 2 diabetes has not been fully established. We investigated the temporal relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), quantitatively assessed the impact, and evaluated the related mediation effect. METHODS: This study involved participants from the China Multi-Ethnic Cohort Study and the UK Biobank. We performed cross-lagged path analysis to compare the relative magnitude of the effects between NAFLD and T2D using two-period biochemical data. Hepatic steatosis and fasting blood glucose elevation (FBG) represented NAFLD and T2D respectively. We fitted two separate Cox proportional-hazards models to evaluate the influence of hepatic steatosis on T2D. Furthermore, we applied the difference method to assess mediation effects. RESULTS: In cross-lagged path analyses, the path coefficients from baseline hepatic steatosis to first repeat FBG (ßCMEC = 0.068, ßUK-Biobank = 0.033) were significantly greater than the path coefficients from baseline FBG to first repeat hepatic steatosis (ßCMEC = 0.027, ßUK-Biobank = -0.01). Individuals with hepatic steatosis have a risk of T2D that is roughly three times higher than those without the condition (HR = 3.478 [3.314, 3.650]). Hepatic steatosis mediated approximately 69.514% of the total effect between obesity and follow-up T2D. CONCLUSIONS: Our findings contribute to determining the sequential relationship between NAFLD and T2D in the causal pathway, highlighting that the dominant pathway in the relationship between these two early stages of diseases was the one from hepatic steatosis to fasting blood glucose elevation. Individuals having NAFLD face a significantly increased risk of T2D and require long-term monitoring of their glucose status as well.

A novel chemical genetic approach reveals paralog-specific role of ERK1/2 in mouse embryonic stem cell fate control.

Introduction: Mouse embryonic stem cell (ESC) self-renewal can be maintained through dual inhibition of GSK3 and MEK kinases. MEK has two highly homologous downstream kinases, extracellular signal-regulated kinase 1 and 2 (ERK1/2). However, the exact roles of ERK1/2 in mouse ESC self-renewal and differentiation remain unclear. Methods: We selectively deleted or inhibited ERK1, ERK2, or both using genetic and chemical genetic approaches combined with small molecule inhibitors. The effects of ERK paralog-specific inhibition on mouse ESC self-renewal and differentiation were then assessed. Results: ERK1/2 were found to be dispensable for mouse ESC survival and self-renewal. The inhibition of both ERK paralogs, in conjunction with GSK3 inhibition, was sufficient to maintain mouse ESC self-renewal. In contrast, selective deletion or inhibition of only one ERK paralog did not mimic the effect of MEK inhibition in promoting mouse ESC self-renewal. Regarding ESC differentiation, inhibition of ERK1/2 prevented mesendoderm differentiation. Additionally, selective inhibition of ERK1, but not ERK2, promoted mesendoderm differentiation. Discussion: These findings suggest that ERK1 and ERK2 have both overlapping and distinct roles in regulating ESC self-renewal and differentiation. This study provides new insights into the molecular mechanisms of ERK1/2 in governing ESC maintenance and lineage commitment, potentially informing future strategies for controlling stem cell fate in research and therapeutic applications.

Highly efficient esterification of carboxylic acids with O-H nucleophiles through acid/iodide cooperative catalysis.

The esterification of carboxylic acids is an important reaction for preparing esters which find wide applications in various research fields. In this manuscript, we report an acid/iodide cooperative catalytic method which enables highly efficient esterification of carboxylic acids with a wide range of equivalent O-H nucleophiles including both alcohols and weak nucleophilic phenols. Under the reaction conditions, both aromatic and aliphatic carboxylic acids including those bearing functional groups work well, furnishing the corresponding esters in good to high yields. Moreover, this reaction is scalable and applicable to the modification of bioactive molecules. These results demonstrate the synthetic value of this new reaction in organic synthesis.

Integrated physiological analyses, transcriptome, and DNA methylation reveal superiority of pear stigma-style complex development regulation.

Styles and stigmas are crucial components of the fertilization process that allows a pear tree to bear fruit. The information regarding the development mechanism of pear style and stigma is still unclear. Our results demonstrated that IAA, ABA, and BR are significantly increased at 1 DBF, while JA is decreased at 5 DBF. The fructose and starch contents significantly increased at 1 DBF when the style with stigma was ready for pollination. Transcriptome and DNA methylation analysis showed 8087 DEGs and 3771 DMRs were enriched in plant hormones biosynthesis, carbohydrate biosynthesis and metabolism, and TFs in 1 DBF as compared with 7 DBF. The CHH methylation type of DMRs accounts for 84.75%. Most DMRs of CHH upregulated in 1 DBF vs. 7 DBF. This study found for the first time that transcription factor ERFs and DNA methylation are involved in regulating the growth and development of fruit plant style and stigma.

Nitro-functionalization on MIL-53(Fe) for PCMX degradation: Elevating Fenton-like catalytic propelled by abundant reaction sites and iron cycle.

To address the issue of excessive residues of 4-chloro-3,5-dimethylphenol (PCMX) in the water environment. In a one-step solvothermal process, iron-based metal-organic frameworks (Fe-MOFs) material MIL-53(Fe) undergoes a synthetic modification strategy. 2-Nitroterephthalic acid as an organic ligand reacted with Fe3+ in a solvothermal process lasting 18 h to yield the nitro-functionalized MIL-53(Fe)-NO2(18h). The objective was to augment the abundance of Fe central unsaturated coordination sites (Fe CUCs) and expedite the Fe(III)/Fe(II) redox cycle, thereby enhancing the heterogeneous Fenton-like treatment capability of pollutants. MIL-53(Fe)-NO2(18h) has excellent hydrogen peroxide (H2O2) catalytic activity and PCMX degradation across a broad pH spectrum (4.0∼8.0). Almost complete removal of PCMX was achieved within 30 min, while pseudo-first-order kinetic rate constants (kobs) increased 4.37 times over MIL-53(Fe). The confirmation of increased Fe CUCs abundance in MIL-53(Fe)-NO2(18h) was achieved through Lewis acidity, oxygen vacancies (OVs) signals, and Fe-O coordination characterization results. Density functional theory (DFT) calculations revealed that Fe CUCs in MIL-53(Fe)-NO2(18h) exhibits heightened affinity for H2O2 adsorption, showcasing stronger charge transfer and enhanced H2O2 dissociation ability. The Fe(III)/Fe(II) redox cycle, a driving force of Fenton-like reactions, was notably improved in the nitro-modified materials. These enhancements significantly expedited the Fenton-like process, resulting in the generation of increased amounts of reactive oxygen species (ROSs), with hydroxyl radicals (OH·) being pivotal components in degradation. The MIL-53(Fe)-NO2(18h)/H2O2 system has demonstrated versatility in treating a variety of emerging contaminants, achieving removal efficiencies exceeding 99.7% for other antibiotics and endocrine disruptors within 60 min. Furthermore, MIL-53(Fe)-NO2(18h) demonstrated outstanding reusability and adaptability in actual water environments. This study introduces a straightforward and environmentally friendly strategy for remediating environmental pollution using Fe-MOF-catalysed heterogeneous Fenton-like technology.

Brainstem Gliomas With Isocitrate Dehydrogenase Mutation: Natural History, Clinical-Radiological Features, Management Strategy, and Long-Term Outcome.

BACKGROUND AND OBJECTIVES: This study aimed to investigate the clinical, radiological, pathological features, treatment options, and outcomes of isocitrate dehydrogenase (IDH)-mutant brainstem gliomas (BSG-IDHmut). METHODS: A retrospective analysis of 22 patients diagnosed with BSG-IDHmut and treated at our institution from January 2011 to January 2017 was performed. Their clinical, radiological data, and long-term outcomes were collected and analyzed. RESULTS: The median age of patients was 38.5 years, with a male predominance (63.6%). All patients had IDH1 and TP53 mutations, with noncanonical IDH mutations in 59.1% of cases, 06-methylguanine-DNA methyltransferase promoter methylation in 55.6%, and alpha-thalassemia mental retardation X-linked loss in 63.2%, respectively. Tumors were primarily located in the pontine-medullary oblongata (54.5%) and frequently involved the pontine brachium (50%). Most tumors exhibited ill-defined boundaries (68.2%), no T2-FLAIR mismatch (100%), and no contrast enhancement (86.3%). Two radiological growth patterns were also identified: focal and extensively infiltrative, which were associated with the treatment strategy when tumor recurred. Seven patients (31.8%) received surgery only and 15 (68.2%) surgery plus other therapy. The median overall survival was 124.8 months, with 1-year, 2-year, 5-year, and 10-year survival rates of 81.8%, 68.2%, 54.5%, and 13.6%, respectively. Six patients experienced tumor recurrence, and all retained their radiological growth patterns, with 2 transformed into central nervous system World Health Organization grade 4. CONCLUSION: BSG-IDHmut represents a unique subgroup of brainstem gliomas with distinctive features and more favorable prognosis compared with other brainstem gliomas. Further research is required to better understand the molecular mechanisms and optimize treatment strategies for this rare and complex disease.

Temporal relationship between hepatic steatosis and blood pressure elevation and the mediation effect in the development of cardiovascular disease.

The temporal relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension remains highly controversial, with ongoing debates on whether NAFLD induces hypertension or vice versa. We employed cross-lagged panel models to investigate the temporal relationship between hepatic steatosis (assessed by Fatty Liver Index [FLI] in the main analysis, and by Proton Density Fat Fraction [PDFF] in the validation study) and blood pressure (systolic and diastolic blood pressure [SBP/ DBP]). Subsequently, we employed causal mediation models to explore the mediation effect in CVD development, including ischemic heart disease and stroke. The main analysis incorporated repeated measurement data of 5,047 participants from the China Multi-Ethnic Cohort (CMEC) and 5,685 participants from the UK Biobank (UKB). In both cohorts, the path coefficients from FLI to blood pressure were significant and greater than the path from blood pressure to FLI, with ßFLI→SBP = 0.081, P < 0.001 versus ßSBP→FLI = 0.020, P = 0.031; ßFLI→DBP = 0.082, P < 0.001 versus ßDBP→FLI = -0.006, P = 0.480 for CEMC, and ßFLI→SBP = 0.057, P < 0.001 versus ßSBP→FLI = -0.001, P = 0.727; ßFLI→DBP = 0.061, P < 0.001, versus ßDBP→FLI = -0.006, P = 0.263 for UKB. The validation study with 962 UKB participants using PDFF consistently supported these findings. In the mediation analyses encompassing 11,108 UKB participants, SBP and DBP mediated 12.2% and 5.2% of the hepatic steatosis-CVD association, respectively. The proportions were lower for ischemic heart disease (SBP: 6.1%, DBP: non-statistically significant -6.8%), and relatively stronger for stroke (SBP: 19.4%, DBP: 26.1%). In conclusion, hepatic steatosis more strongly contributes to elevated blood pressure than vice versa. Blood pressure elevation positively mediates the hepatic steatosis-CVD association, particularly in stroke compared to ischemic heart disease.

The Insular Cortex: An Interface Between Sensation, Emotion and Cognition.

The insula is a complex brain region central to the orchestration of taste perception, interoception, emotion, and decision-making. Recent research has shed light on the intricate connections between the insula and other brain regions, revealing the crucial role of this area in integrating sensory, emotional, and cognitive information. The unique anatomical position and extensive connectivity allow the insula to serve as a critical hub in the functional network of the brain. We summarize its role in interoceptive and exteroceptive sensory processing, illustrating insular function as a bridge connecting internal and external experiences. Drawing on recent research, we delineate the insular involvement in emotional processes, highlighting its implications in psychiatric conditions, such as anxiety, depression, and addiction. We further discuss the insular contributions to cognition, focusing on its significant roles in time perception and decision-making. Collectively, the evidence underscores the insular function as a dynamic interface that synthesizes diverse inputs into coherent subjective experiences and decision-making processes. Through this review, we hope to highlight the importance of the insula as an interface between sensation, emotion, and cognition, and to inspire further research into this fascinating brain region.

The Trends of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Systemic Immunoinflammatory Index in Patients with Intracerebral Hemorrhage and Clinical Value in Predicting Pneumonia 30 Days After Surgery.

BACKGROUND: Inflammatory response is closely associated with secondary brain injury and pneumonia in intracerebral hemorrhage (ICH). In this study, we aimed to investigate the value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immunoinflammatory index (SII) in the development of pneumonia in ICH patients 30 days after surgery. METHODS: We retrospectively collected clinical data on patients with ICH who underwent surgical treatment at our institution from January 2016 to December 2022, mainly including NLR, PLR, and SII at different time points. Receiver operating characteristic curves were used to compare the value of different inflammatory indicators in predicting the development of postoperative pneumonia 30 days after surgery in ICH patients, and multivariate logistic regression analyses were used to identify independent risk factors for pneumonia 30 days after surgery. RESULTS: Among 112 patients with ICH undergoing surgical treatment, 31 (27.7%) developed pneumonia postoperatively. The results of the univariate analysis demonstrated that patients in the pneumonia group experienced significantly higher blood glucose, NLR at 72 hours postoperatively, PLR at 72 hours postoperatively, and SII at 72 hours postoperatively (SII3) than those in the nonpneumonia group, and significantly lower admission Glasgow Coma Scale scores than those in the nonpneumonia group (all P < 0.05). NLR, PLR, and SII showed increasing and then decreasing in the disease process of ICH and peaked at 48 hours postoperatively. Multivariable logistic regression analysis revealed that SII3 was an independent risk factor for postoperative pneumonia 30 days after surgery in ICH patients (odds ratio = 1.001, 95% confidence interval: 1.000-1.002, P = 0.008). The area under the curve of the developed nomogram model was 0.895 (95% confidence interval = 0.823-0.967), with a sensitivity and specificity of 0.903 and 0.815, respectively, providing good predictive power. CONCLUSIONS: In the course of ICH, NLR, PLR, and SII increased and then decreased and peaked at 48 hours postoperatively. The SII3 was the best predictor of the occurrence of pneumonia postoperatively in ICH patients.

[Alcohol Abstinence and Accelerated Biological Aging Among Middle-Aged and Older Adults: Evidence From the UK Biobank]. / ä¸­è€å¹´ç¾¤ä½“é ’ç²¾æˆ’æ–­ä¸Žç”Ÿç‰©è¡°è€åŠ é€Ÿçš„å ³ç³»ï¼šåŸºäºŽè‹±å›½ç”Ÿç‰©é“¶è¡Œæ•°æ®åº“çš„ç ”ç©¶.

Objective: To investigate the longitudinal association between alcohol abstinence and accelerated biological aging among middle-aged and older adults and to explore the potential effect modifiers influencing the association. Methods: Utilizing the clinico-biochemical and anthropometric data from the baseline and first repeat survey of the UK Biobank (UKB), we employed the Klemera and Doubal method (KDM) to construct the biological age (BA) and calculate BA acceleration. Change analysis based on multivariate linear regression models was employed to explore the association between changes in alcohol abstinence and changes in BA acceleration. Age, sex, smoking status, tea and coffee consumption, and body mass index were considered as the stratification factors for conducting stratified analysis. Results: A total of 5 412 participants were included. Short-term alcohol abstinence (ß=1.00, 95% confidence interval [CI]: 0.15-1.86) was found to accelerate biological aging when compared to consistent never drinking, while long-term abstinence (ß=-0.20, 95% CI: -1.12-0.71) did not result in a significant acceleration of biological aging. Body mass index may be a potential effect modifier. Conclusion: Short-term alcohol abstinence was associated with accelerated biological aging, but the effect gradually diminishes over extended periods of abstinence.