A nonneural miRNA cluster mediates hearing via repression of two neural targets.

We show here that mir-279/996 are absolutely essential for development and function of Johnston's organ (JO), the primary proprioceptive and auditory organ in Drosophila Their deletion results in highly aberrant cell fate determination, including loss of scolopale cells and ectopic neurons, and mutants are electrophysiologically deaf. In vivo activity sensors and mosaic analyses indicate that these seed-related miRNAs function autonomously to suppress neural fate in nonneuronal cells. Finally, genetic interactions pinpoint two neural targets (elav and insensible) that underlie miRNA mutant JO phenotypes. This work uncovers how critical post-transcriptional regulation of specific miRNA targets governs cell specification and function of the auditory system.

Dynamic immunoediting by macrophages in homologous recombination deficiency-stratified pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully understanding the distinct characteristics and implications of HRD-associated PDAC. We analyzed 16 PDAC patient-derived tissues, categorized by their homologous recombination deficiency (HRD) scores, and performed high-plex immunofluorescence analysis to define 20 cell phenotypes, thereby generating an in-situ PDAC tumor-immune landscape. Spatial phenotypic-transcriptomic profiling guided by regions-of-interest (ROIs) identified a crucial regulatory mechanism through localized tumor-adjacent macrophages, potentially in an HRD-dependent manner. Cellular neighborhood (CN) analysis further demonstrated the existence of macrophage-associated high-ordered cellular functional units in spatial contexts. Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC.

Quantitative Real-Time Analysis of Living Materials by Stimulated Raman Scattering Microscopy.

Composite materials built in part from living organisms have the potential to exhibit useful autonomous, adaptive, and self-healing behavior. The physicochemical, biological, and mechanical properties of such materials can be engineered through the genetic manipulation of their living components. Successful development of living materials will require not only new methods for design and preparation but also new analytical tools that are capable of real-time noninvasive mapping of chemical compositions. Here, we establish a strategy based on stimulated Raman scattering microscopy to monitor phosphatase-catalyzed mineralization of engineered bacterial films in situ. Real-time label-free imaging elucidates the mineralization process, quantifies both the organic and inorganic components of the material as functions of time, and reveals spatial heterogeneity at multiple scales. In addition, we correlate the mechanical performance of films with the extent of mineralization. This work introduces a promising strategy for quantitatively analyzing living materials, which should contribute to the accelerated development of such materials in the future.

Construction of Hierarchical Conductive Networks for LiNi0.8Mn0.1Co0.1O2 Cathode toward Stable Cycling at High Areal Mass Loadings.

Realizing high-performance thick electrodes is considered as a practical strategy to promote the energy density of lithium-ion batteries. However, establishing effective transport pathways for both lithium-ions and electrons in a thick electrode is very challenging. This study develops a hierarchical conductive network structure for constructing high-performance NMC811 (LiNi0.8Mn0.1Co0.1O2) cathode toward stable cycling at high areal mass loadings. The hierarchical conductive networks are composed of a Li+/e- mixed conducting interface (lithium polyacrylate/hydroxyl-functionalized multiwalled carbon nanotubes) on NMC811 particles, and a segregated network of single-walled carbon nanotubes in the electrode, without any additional binders or carbon black. Such strategy endows the NMC811 cathode (up to 250 µm and 50 mg cm-2) with low porosity/tortuosity, ultrahigh Li+/e- conductivities and excellent mechanical property at low carbon nanotube content (1.8 wt%). It significantly improves the electrochemical reaction homogeneity along the electrode depth, meanwhile effectively inhibits the side reactions at the electrode/electrolyte interface and cracks in the NMC particles during cycling. This work emphasizes the crucial role of the electronic/ionic cooperative transportation in the performance deterioration of thick cathodes, and provide guidance for architecture optimization and performance improvement of thick electrodes toward practical applications, not just for the NMC811 cathode.

Development of a Novel Prediction Tool for Response to First-Line Treatments of Monosymptomatic Nocturnal Enuresis: A Randomized, Controlled, International, Multicenter Study (DRYCHILD).

PURPOSE: Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of these together with other demographic and clinical variables for response to first-line treatments in children with MNE. MATERIALS AND METHODS: A randomized, controlled, international, multicenter study was conducted in 324 treatment-naïve children (6-14 years old) with primary MNE. The children were randomized to treatment with or without prior consideration of voiding diaries. In the group where treatment choice was based on voiding diaries, children with nocturnal polyuria and normal maximum voided volume (MVV) received desmopressin (dDAVP) treatment, and children with reduced MVV and no nocturnal polyuria received an enuresis alarm. In the other group, treatment with dDAVP or alarm was randomly allocated. RESULTS: A total of 281 children (72% males) were qualified for statistical analysis. The change of responding to treatment was 21% higher in children where treatment was individualized compared to children where treatment was randomly selected (risk ratio = 1.21 [1.02-1.45], P = .032). In children with reduced MVV and no nocturnal polyuria (35% of all children), individualized treatment was associated with a 46% improvement in response compared to random treatment selection (risk ratio = 1.46 [1.14-1.87], P = .003). Furthermore, we developed a clinically relevant prediction model for response to dDAVP treatment (receiver operating characteristic curve 0.85). CONCLUSIONS: The present study demonstrates that treatment selection based on voiding diaries improves response to first-line treatment, particularly in specific subtypes. Information from voiding diaries together with clinical and demographic information provides the basis for predicting response. CLINICAL TRIAL REGISTRATION NO.: NCT03389412.

Enhanced response over wavelength range of 7-12 µm for quantum wells in asymmetric micro-pillars.

Efficient coupling in broad wavelength range is desirable for wide-spectrum infrared light detection, yet this is a challenge for intersubband transition in semiconductor quantum wells (QWs). High-Q cavities mostly intensify the absorption at peak wavelengths but with shrinking bandwidth. Here, we propose a novel approach to expand the operating spectral range of the Quantum Well Infrared Photodetectors (QWIPs). By processing the QWs into asymmetric micro-pillar array structure, the device demonstrates a substantial enhancement in spectral response across the wavelength from 7.1 µm to 12.3 µm with guided mode resonance (GMR) effects. The blackbody responsivity is then increased by 3 times compared to that of the 45° polished edge-coupled counterpart. Meanwhile, the dark current density remains unchanged after the deep etching process, which will benefit the electrical performance of the detector with reduced volume duty ratio. In contrast to the symmetric micro-pillar array that contains simple resonance mode, the detectivity of QWIP in asymmetric pillar structure is found to be improved by 2-4 times within the range of 9.5 µm to 15 µm.

Boosting Catalytic and Anti-fluorination Performance of the Ru/Vanadia-Titania Catalyst for the Oxidative Destruction of Freon by Sulfuric Acid Modification.

Chlorofluorocarbons (CFCs) exert a strong greenhouse effect and constitute the largest contributor to ozone depletion. Catalytic removal is considered an effective pathway for eliminating low-concentration CFCs under mild conditions. The key issue is the easy deactivation of the catalysts due to their surface fluorination. We herein report a comparative investigation on catalytic dichlorodifluoromethane (CFC-12) removal in the absence or presence of water over the sulfuric-acid-modified three-dimensionally ordered macroporous vanadia-titania-supported Ru (S-Ru/3DOM VTO) catalysts. The S-Ru/3DOM VTO catalyst exhibited high activity (T90% = 278 °C at space velocity = 40 000 mL g-1 h-1) and good stability within 60 h of on-stream reaction in the presence of 1800 ppm of water due to the improvements in acid site amount and redox ability that promoted the adsorption of CFC-12 and the activation of C-F bonds. Compared with the case under dry conditions, catalytic performance for CFC-12 removal was better over the S-Ru/3DOM VTO catalyst in the presence of water. Water introduction mitigated surface fluorination by the replenishment of hydroxyl groups, inhibited the formation of halogenated byproducts via the surface fluorine species cleaning effect, and promoted the reaction pathway of COX2 (X = Cl/F) → carboxylic acid → CO2.

Assessment of the 2023 European Kidney Function Consortium (EKFC) equations in a Chinese adult population.

OBJECTIVES: The European Kidney Function Consortium (EKFC) developed two novel equations in 2023 for estimating glomerular filtration rate (GFR): one sex-free cystatin C-based equation (EKFCCys) and one creatinine-cystatin C combined equation (EKFCCr-Cys). This study compared their performance with the previous creatinine-based EKFC equation (EKFCCr) and commonly used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study (BIS) equations in Chinese adults. METHODS: A total of 2,438 Chinese adults (mean age=53.04 years) who underwent the 99mTc-DTPA renal dynamic imaging for reference GFR (rGFR) were included. Diagnostic value was evaluated using correlation coefficients, sensitivity, specificity, and area under the receiver operating characteristic curve (ROCAUC). Performance was assessed in terms of bias, precision (interquartile range of the median difference [IQR]), accuracy (percentage of estimates ±30 % of rGFR [P30], and root-mean-square error [RMSE]) across age, sex, and rGFR subgroups. Gender differences in bias and P30 were also analyzed. RESULTS: Average rGFR was 73.37 mL/min/1.73 m2. EKFC equations showed stronger correlations and larger AUCs compared to the parallel CKD-EPI equations, with EKFCCr-Cys demonstrating the greatest improvement (R=0.771, ROCAUC=0.913). Concerning bias, precision, and accuracy, EKFC equations consistently outperformed CKD-EPI equations. EKFCCr-Cys and EKFCCr performed acceptably well in the entire population and were equivalent to BIS equations in the elderly. All equations, including EKFCCys, showed similar P30 accuracy across sexes. CONCLUSIONS: EKFC equations provided a reasonable alternative for estimating GFR in the Chinese adult population. While EKFCCys did not outperform EKFCCr, EKFCCr-Cys improved the accuracy of single-marker equations.

Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values.

OBJECTIVES: Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. METHODS: We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20 % [P20] and ±30 % [P30] of rGFR). RESULTS: RIs for males were: 18-79 years, 55.53-92.50 µmol/L; ≥80 years, 54.41-96.43 µmol/L. RIs for females were: 18-59 years, 40.42-69.73 µmol/L; 60-79 years, 41.16-73.69 µmol/L; ≥80 years, 46.50-73.20 µmol/L. Q-values were set at 73.82 µmol/L (0.84 mg/dL) for males and 53.80 µmol/L (0.61 mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. CONCLUSIONS: We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.

Correlation Between Impaired Sensitivity to Thyroid Hormones and Serum Uric Acid in Female Patients With Obesity and After Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: An alterable risk factor for hyperuricemia is obesity. Additionally, obese people may have a moderate form of acquired resistance to thyroid hormones. Thyrotropin, thyroid hormones, and obesity all interact subtly. However, the connection between thyroid hormone sensitivity and hyperuricemia in obese patients both before and after laparoscopic sleeve gastrectomy (LSG) has not yet been clarified. The objective of our study was to investigate the connection between impaired thyroid hormone sensitivity and elevated uric acid (UA) levels before and after LSG. METHODS: In total, 1054 euthyroid patients with obesity (481 males, 573 females), 248 (143 female patients) of whom underwent subsequent LSG, were enrolled in this retrospective study. Anthropometric measurements and thyroid hormone and UA levels were taken before and 3 months after LSG. RESULTS: Female patients with obesity with impaired sensitivity to thyroid hormones had higher UA levels (P for trend <.01). The odds ratio of the fourth vs first quartile of thyroid feedback quantile index, thyrotropin index, and thyrotropin-thyroxine resistance index were 4.285 (confidence interval: 1.360-13.507), 3.700 (confidence interval: 1.276-10.729), and 2.839 (confidence interval: 1.014-7.948), respectively, with robust relationships with female hyperuricemia (all P < .05). However, there was only a positive correlation between the decline in UA levels and thyroid feedback quantile index, thyrotropin, and thyrotropin-thyroxine resistance index in female patients following LSG. CONCLUSION: Female hyperuricemia is correlated with higher thyroid hormone resistance index scores. Resistance to thyroid hormones was greatly improved by LSG. The decrease in UA levels after surgery is correlated with the improvement of thyroid hormone resistance after LSG.

Application of robot navigation system for insertion of femoral neck system in the treatment of femoral neck fracture.

PURPOSE: To evaluate the short-term clinical efficacy and advantages of surgery robot positioning system for insertion of Femoral Neck System (FNS) in the treatment of femoral neck fractures. METHODS: The clinical data of 52 patients with Femoral neck fracture (FNF) who had been treated with FNS between June 2020 and September 2021 were retrospectively analyzed. Among them, 26 patients were treated with traditional FNS (control group), while 26 additional patients were treated with FNS assisted by an orthopaedic robot positioning system (study group). The operation duration, frequency of key-guide needle placement, intraoperative blood loss, incision length, fracture healing rate, fracture healing time, and the Harris scores at the last follow-up were calculated and compared between the 2 groups. RESULTS: The study group had shorter operation duration, fewer numbers of placing the key-guide needle, less intraoperative blood loss, and smaller surgical incisions than the control group (all, P < 0.05). There was no significant difference in the rate of fracture healing rate between the 2 groups (P = 0.47), while the fracture healing duration of the study group was shorter than that of the control group (P = 0.03). At the last follow-up, compared with the control group, the Harris score and the number of excellent and good ratings were significantly higher in the study group (all, P < 0.05). CONCLUSIONS: Using orthopaedic surgery robot positioning system-assisted FNS in the treatment of FNFs can effectively improve the efficiency of surgery, shorten operation time, and reduce the number of placing the key-guide needle, intraoperative blood loss, and operative trauma. Simultaneously, it shortens the duration of fracture healing and improves the recovery of hip function.

Retrospecting Digital Media Use, Negative Emotions, and Trust Gaps During the COVID-19 Pandemic in China: Cross-Sectional Web-Based Survey.

BACKGROUND: Retrospecting the trust gaps and their dynamics during the pandemic is crucial for understanding the root causes of postpandemic challenges and offers valuable insights into preparing for future public health emergencies. The COVID-19 pandemic eroded people's trust in strangers and acquaintances, while their trust in family members remained relatively stable. This resulted in 2 trust gaps, namely, the family members-strangers trust gap and the family members-acquaintances trust gap. Widening trust gaps impede social integration and undermine the effective management of public health crises. However, little is known about how digital media use shaped trust gaps during a pandemic. OBJECTIVE: This study aims to investigate the relationships between digital media use, negative emotions, the family members-strangers trust gap, and the family members-acquaintances trust gap during the COVID-19 pandemic in China. We test the mediating role of negative emotions between digital media use and 2 trust gaps and compare the indirect effect of digital media use on 2 trust gaps through negative emotions. METHODS: A cross-sectional web-based survey was conducted in China between January 31, 2020, and February 9, 2020. A total of 1568 adults participated in the survey. Questions related to digital media use, negative emotions, trust in family members, trust in acquaintances, and trust in strangers during the pandemic were asked. Regression analyses were performed to test the associations between the examined variables. We used a 95% bootstrap CI approach to estimate the mediation effects. RESULTS: Digital media use was positively associated with negative emotions (B=0.17, SE 0.03; P<.001), which in turn were positively associated with the family members-strangers trust gap (B=0.15, SE 0.03; P<.001). Likewise, digital media use was positively associated with negative emotions (B=0.17, SE 0.03; P<.001), while negative emotions were positively associated with the family members-acquaintances trust gap (B=0.08, SE 0.03; P=.01). Moreover, the indirect effect of digital media use on the family members-strangers trust gap (B=0.03, SE 0.01; 95% CI 0.01-0.04) was stronger than that on the family members-acquaintances trust gap (B=0.01, SE 0.01; 95% CI 0.003-0.027). CONCLUSIONS: The results demonstrate that negative emotions resulting from the frequent use of digital media are a key factor that accounts for the widening trust gaps. Considering the increasing reliance on digital media, the findings indicate that the appropriate use of digital media can prevent the overamplification of negative emotions and curb the enlargement of trust gaps. This may help restore social trust and prepare for future public health crises in the postpandemic era.

Metabonomics and Transcriptomic Analysis of Free Fatty Acid Synthesis in Seedless and Tenera Oil Palm.

Oil palm, a tropical woody oil crop, is widely used in food, cosmetics, and pharmaceuticals due to its high production efficiency and economic value. Palm oil is rich in free fatty acids, polyphenols, vitamin E, and other nutrients, which are beneficial for human health when consumed appropriately. Therefore, investigating the dynamic changes in free fatty acid content at different stages of development and hypothesizing the influence of regulatory genes on free fatty acid metabolism is crucial for improving palm oil quality and accelerating industry growth. LC-MS/MS is used to analyze the composition and content of free fatty acids in the flesh after 95 days (MS1 and MT1), 125 days (MS2 and MT2), and 185 days (MS3 and MT3) of Seedless (MS) and Tenera (MT) oil palm species fruit pollination. RNA-Seq was used to analyze the expression of genes regulating free fatty acid synthesis and accumulation, with differences in genes and metabolites mapped to the KEGG pathway map using the KEGG (Kyoto encyclopedia of genes and genomes) enrichment analysis method. A metabolomics study identified 17 types of saturated and 13 types of unsaturated free fatty acids during the development of MS and MT. Transcriptomic research revealed that 10,804 significantly different expression genes were acquired in the set differential gene threshold between MS and MT. The results showed that FabB was positively correlated with the contents of three main free fatty acids (stearic acid, myristate acid, and palmitic acid) and negatively correlated with the contents of free palmitic acid in the flesh of MS and MT. ACSL and FATB were positively correlated with the contents of three main free fatty acids and negatively correlated with free myristate acid. The study reveals that the expression of key enzyme genes, FabB and FabF, may improve the synthesis of free myristate in oil palm flesh, while FabF, ACSL, and FATB genes may facilitate the production of free palmitoleic acid. These genes may also promote the synthesis of free stearic acid and palmitoleic acid in oil palm flesh. However, the FabB gene may inhibit stearic acid synthesis, while ACSL and FATB genes may hinder myristate acid production. This study provides a theoretical basis for improving palm oil quality.

Square Root Statistics of Density Matrices and Their Applications.

To estimate the degree of quantum entanglement of random pure states, it is crucial to understand the statistical behavior of entanglement indicators such as the von Neumann entropy, quantum purity, and entanglement capacity. These entanglement metrics are functions of the spectrum of density matrices, and their statistical behavior over different generic state ensembles have been intensively studied in the literature. As an alternative metric, in this work, we study the sum of the square root spectrum of density matrices, which is relevant to negativity and fidelity in quantum information processing. In particular, we derive the finite-size mean and variance formulas of the sum of the square root spectrum over the Bures-Hall ensemble, extending known results obtained recently over the Hilbert-Schmidt ensemble.

Association of systemic inflammation response index with all-cause mortality as well as cardiovascular mortality in patients with chronic kidney disease.

Background: Chronic Kidney Disease (CKD) stands as a formidable health challenge, recognized not only for its growing prevalence but also for its association with elevated mortality rates. Emerging evidence suggests that CKD is inherently linked to inflammatory processes, marking it as an inflammatory disorder. In this landscape, the systemic inflammatory response index (SIRI) emerges as a novel inflammation marker, yet to be applied for assessing the risk of mortality in CKD patients. Objective: This study aims to investigate the prognostic significance of the SIRI in all-cause and cardiovascular disease (CVD) mortality among patients with CKD. Method: This study conducted a retrospective observational study using the National Health and Nutrition Examination Survey (NHANES) database, encompassing data from 1999 to 2018. This analysis included 9,115 CKD patients, categorized based on SIRI quartiles. Key outcomes were all-cause and CVD mortality, analyzed using Kaplan-Meier survival curves, restricted cube splines (RCS) and cox proportional hazards models. Result: In this study of 9,115 CKD patients, the Kaplan-Meier survival analysis revealed a greater incidence of all-cause death among groups with higher SIRI (P-log rank <0.001). In the fully adjusted model (Model 3), each unit increase in SIRI led to a 20% increase in the risk of all-cause mortality. Additionally, higher SIRI quartiles (Q3 and Q4) were associated with increased risk compared to the lowest quartile (Q1) (Q3: HR: 1.16, 95% CI: 1.01-1.34; Q4: HR: 1.63, 95% CI: 1.40-1.90; P for trend <0.001). Similarly, for CVD mortality, each unit increase in SIRI in Model 3 increased the risk by 33%, with Q3 and Q4 showing higher risk than Q1 (Q3: HR: 1.39, 95% CI: 1.11-1.70; Q4: HR: 2.26, 95% CI: 1.72-2.98; P for trend <0.001). Conclusion: SIRI was positively associated with all-cause and CVD mortality in patients with CKD.

Mapping the evolution of acne research based on 100 top-cited articles: A bibliometric analysis of trends and hotspots from 2014 to 2023.

BACKGROUND: Acne is a prevalent inflammatory condition of the pilosebaceous unit, which seriously affects the appearance and mental health of patients. Bibliometrics is the statistical analysis of academic literature in a certain field. We aimed to characterize the 100 most cited articles on acne from a bibliometric perspective, as well as explore the frontier hotspots and trends of acne. METHODS: A search was conducted on the Web of Science database on August 8, 2023. we employed the terms "acne," "acne Vulgaris," and "common acne" in our search. The top 100 articles with the most citations throughout the time frame of 2014 to 2023 were discovered and assessed. The visualization study was carried out using bibliometric tools such as CiteSpace 6.2.R4, VOSviewer 1.6.18, and MapChart. RESULTS: The top 100 most cited articles were published between 2014 and 2021, originated from a diverse range of 48 countries, with a predominant focus on the United States of America (USA) and Germany. The top 100 papers were cited between 50 and 712 times. Dreno B, from Nantes University, was the most frequently nominated author. With 12 papers, the Journal of the European Academy of Dermatology and Venereology contributed the most to the top 100 list. Alongside the term "acne", the following terms or phrases were observed frequency in the top 100 articles, Cutibacterium acnes, sebaceous, western diet, antibiotic resistance, staphylococcus-epidermidis, insulinlike growth factor 1, benzoyl peroxide, and polyunsaturated fatty acids. Alongside the term "acne", terms or phrases such as Cutibacterium acnes, sebaceous, western diet, antibiotic resistance, staphylococcus-epidermidis, insulinlike growth factor 1, benzoyl peroxide, and polyunsaturated fatty acids, etc also have a high frequency in the top 100 articles. CONCLUSION: This analysis summarizes the shifting trends of acne research over the last decades. Research on acne is currently flourishing. The related pathogenesis and therapeutic strategies have been the focus of current research and developmental trends in future research.

Network Pharmacology Prediction and Molecular Docking-Based Strategy to Explore the Potential Mechanism of Gualou Xiebai Banxia Decoction against Myocardial Infarction.

The aim of this study was to investigate targets through which Gualou Xiebai Banxia decoction aids in treating myocardial infarction (MI) using network pharmacology in combination with molecular docking. The principal active ingredients of Gualou Xiebai Banxia decoction were identified from the TCMSP database using the criteria of drug-likeness ≥30% and oral bioavailability ≥0.18. Interactions and pathway enrichment were investigated using protein-protein interaction (PPI) networks and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, respectively. Active component structures were docked with those of potential protein targets using AutoDock molecular docking relative softwares. HIF1A was of particular interest as it was identified by the PPI network, GO and KEGG pathway enrichment analyses. In conclusion, the use of network pharmacology prediction and molecular docking assessments provides further information on the active components and mechanisms of action Gualou Xiebai Banxia decoction.

Regulation of T cells in the tumor microenvironment by histone methylation: LSD1 inhibition-a new direction for enhancing immunotherapy.

Although immune checkpoint blockade (ICB) has been shown to achieve durable therapeutic responses in various types of tumors, only 20-40 % of patients benefit from this therapy. A growing body of research suggests that epigenetic modulation of the tumor microenvironment may be a promising direction for enhancing the efficacy of immunotherapy, for example, histone methylation plays an important role in the regulation of T cells in the tumor microenvironment (TME). In particular, histone lysine-specific demethylase 1 (LSD1/KDM1A), as an important histone-modifying enzyme in epigenetics, was found to be an important factor in the regulation of T cells. Therefore, this paper will summarize the effects of histone methylation, especially LSD1, on T cells in the TME to enhance the efficacy of anti-PD-1 immunotherapy. To provide a strong theoretical basis for the strategy of combining LSD1 inhibitors with anti-PD-1/PD-L1 immunotherapy, thus adding new possibilities to improve the survival of tumor patients.

Risk assessment of land subsidence based on GIS in the Yongqiao area, Suzhou City, China.

This study focuses on the Yongqiao District in Suzhou City, Anhui Province, China, aiming to analyze the current situation of ground settlement and its influencing factors in the area. The selected risk indices include settlement rate, cumulative settlement amount, groundwater level drop funnel, thickness of loose sediment layer, thickness of soft soil layer, and the number of groundwater extraction layers. Additionally, vulnerability indices such as population density, building density, road traffic, and functional zoning are considered. An evaluation index system for assessing land Subsidence risk was established. The risk evaluation of land Subsidence was conducted using the Hierarchical analysis-composite index method and ArcGIS spatial analysis, The evaluation results show that the area of higher risk area is about 2.82 km2, accounting for 0.96% of the total area, mainly distributed in the area of Jiuli village, Sanba Street. The middle risk area is distributed around the higher area, with an area of about 9.18 km2, accounting for 3.13% of the total area. The lower risk areas were distributed in most of the study area, covering an area of 222.24 km2, accounting for 75.82% of the total area. The low risk assessment area is mainly distributed in Bianhe Street and part of Zhuxianzhuang Town, with an area of about 58.88 km2, accounting for 20.09% of the total area. The findings of this study are not only crucial for informing local policies and practices related to land use planning, infrastructure development, and emergency response but also enhance our understanding of the complexities of land Subsidence processes and their interactions with human activities, informing future research and practice in environmental risk assessment and management.

Nitrile Vibrational Lifetimes as Probes of Local Electric Fields.

Optical measurements of electric fields have wide-ranging applications in the fields of chemistry and biology. Previously, such measurements focused on shifts in intensity or frequency. Here, we show that nitrile vibrational lifetimes can report local electric fields through ultrasensitive picosecond mid-infrared-near-infrared double-resonance fluorescence spectro-microscopy on Rhodamine 800. Using a robust convolution fitting approach, we observe that the nitrile vibrational lifetimes are strongly linearly correlated (R2 = 0.841) with solvent reaction fields. Supported by density functional theory, we rationalize this trend through a doorway model of intramolecular vibrational energy redistribution. This work provides new fundamental insights into the nature of vibrational energy flow in large polyatomic molecular systems and establishes a theoretical basis for electric field sensing with vibrational lifetimes, offering a new experimental dimension for probing intracellular electrostatics.