Target Cell Extraction and Spectrum-Effect Relationship Coupled with BP Neural Network Classification for Screening Potential Bioactive Components in Ginseng Extract with a Protective Effect against Myocardial Damage.

Cardiovascular disease has become a common ailment that endangers human health, having garnered widespread attention due to its high prevalence, recurrence rate, and sudden death risk. Ginseng possesses functions such as invigorating vital energy, enhancing vein recovery, promoting body fluid and blood nourishment, calming the nerves, and improving cognitive function. It is widely utilized in the treatment of various heart conditions, including palpitations, chest pain, heart failure, and other ailments. Although numerous research reports have investigated the cardiovascular activity of single ginsenoside, there remains a lack of systematic research on the specific components group that predominantly contribute to cardiovascular efficacy in ginseng medicinal materials. In this research, the spectrum-effect relationship, target cell extraction, and BP neural network classification were used to establish a rapid screening system for potential active substances. The results show that red ginseng extract (RGE) can improve the decrease in cell viability and ATP content and inhibit the increase in ROS production and LDH release in OGD-induced H9c2 cells. A total of 70 ginsenosides were identified in RGE using HPLC-Q-TOF-MS/MS analysis. Chromatographic fingerprints were established for 12 batches of RGE by high-performance liquid chromatography (HPLC). A total of 36 common ingredients were found in 12 batches of RGE. The cell viability, ATP, ROS, and LDH of 12 batches RGE were tested to establish gray relationship analysis (GRA) and partial least squares discrimination analysis (PLS-DA). BP neural network classification and target cell extraction were used to narrow down the scope of Spectral efficiency analysis and screen the potential active components. According to the cell experiments, RGE can improve the cell viability and ATP content and reduce the oxidative damage. Then, seven active ingredients, namely, Ginsenoside Rg1, Rg2, Rg3, Rb1, Rd, Re, and Ro, were screened out, and their cardiovascular activity was confirmed in the OGD model. The seven ginsenosides were the main active substances of red ginseng in treating myocardial injury. This study offers a reference for quality control in red ginseng and preparations containing red ginseng for the management of cardiovascular diseases. It also provides ideas for screening active ingredients of the same type of multi-pharmacologically active traditional Chinese medicines.

In situ cleaning of foulants by gas scouring on the membrane-electrode in an electro-membrane bioreactor.

Low-maintenance membrane cleaning is essential for the stable operation of membrane bioreactors. This work proposes an in-situ electrical-cleaning method using an electro-MBR. When the applied bias was transiently increased, the membrane flux recovered rapidly because of the scouring effect from gas evolution reactions. The exfoliation of the cake layer induced by gas scouring played a major role in mitigating membrane fouling, recovering the transmembrane pressure (TMP) by 88.6 % under optimal conditions. Membrane modules did not require replacement during the operation period due to the efficacy of electrical cleaning, with the TMP varying between 37.5 % and 62.5 % of the ultimate pressure requiring change of the membrane modules. Despite the increase in power consumption of 0.66 Wh·m-3 due to the additional applied bias, there was no need for chemical additives or manual maintenance. Therefore, the electrical cleaning method enhanced the service life and reduced the maintenance costs of the electro-MBR.

A new threshold selection method for species distribution models with presence-only data: Extracting the mutation point of the P/E curve by threshold regression.

Selecting thresholds to convert continuous predictions of species distribution models proves critical for many real-world applications and model assessments. Prevalent threshold selection methods for presence-only data require unproven pseudo-absence data or subjective researchers' decisions. This study proposes a new method, Boyce-Threshold Quantile Regression (BTQR), to determine thresholds objectively without pseudo-absence data. We summarize that the mutation point is a typical shape feature of the predicted-to-expected (P/E) curve after reviewing relevant articles. Analysis based on source-sink theory suggests that this mutation point may represent a transition in habitat types and serve as an appropriate threshold. Threshold regression is introduced to accurately locate the mutation point. To validate the effectiveness of BTQR, we used four virtual species of varying prevalence and a real species with reliable distribution data. Six different species distribution models were employed to generate continuous suitability predictions. BTQR and nine other traditional methods transformed these continuous outputs into binary results. Comparative experiments show that BTQR has advantages in terms of accuracy, applicability, and consistency over the existing methods.

Discovery of Natural Products Alleviating Renal Fibrosis with a Viscosity-Responsive Molecular Probe.

Renal fibrosis poses a significant threat to individuals suffering from chronic progressive kidney disease. Given the absence of effective medications for treating renal fibrosis, it becomes crucial to assess the extent of fibrosis in real time and explore the development of novel drugs with substantial therapeutic benefits. Due to the accumulation of renal tissue damage and the uncontrolled deposition of fibrotic matrix during the course of the disease, there is an increase in viscosity both intracellularly and extracellularly. Therefore, a viscosity-sensitive near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging probe, BDP-KY, was developed to detect aberrant changes in viscosity during fibrosis. Furthermore, BDP-KY has been applied to screen the effective components of herbal medicine, rhubarb, resulting in the identification of potential antirenal fibrotic compounds such as emodin-8-glucoside and chrysophanol 8-O-glucoside. Ultrasound, PA, and NIRF imaging of a unilateral uretera obstruction mice model show that different concentrations of emodin-8-glucoside and chrysophanol 8-O-glucoside effectively reduce viscosity levels during the renal fibrosis process. The histological results showed a significant decrease in fibrosis factors α-smooth muscle actin and collagen deposition. Combining these findings with their pharmacokinetic characteristics, these compounds have the potential to fill the current market gap for effective antirenal fibrosis drugs. This study demonstrates the potential of BDP-KY in the evaluation of renal fibrosis, and the two identified active components from rhubarb hold great promise for the treatment of renal fibrosis.

A patent review on HMGB1 inhibitors for the treatment of liver diseases.

INTRODUCTION: HMGB1 is a non-histone chromatin protein released or secreted in response to tissue damage or infection. Extracellular HMGB1, as a crucial immunomodulatory factor, binds with several different receptors to innate inflammatory responses that aggravate acute and chronic liver diseases. The increased levels of HMGB1 have been reported in various liver diseases, highlighting that it represents a potential biomarker and druggable target for therapeutic development. AREAS COVERED: This review summarizes the current knowledge on the structure, function, and interacting receptors of HMGB1 and its significance in multiple liver diseases. The latest patented and preclinical studies of HMGB1 inhibitors (antibodies, peptides, and small molecules) for liver diseases are summarized by using the keywords 'HMGB1,' 'HMGB1 antagonist, HMGB1-inhibitor,' 'liver disease' in Web of Science, Google Scholar, Google Patents, and PubMed databases in the year from 2017 to 2023. EXPERT OPINIONS: In recent years, extensive research on HMGB1-dependent inflammatory signaling has discovered potent inhibitors of HMGB1 to reduce the severity of liver injury. Despite significant progress in the development of HMGB1 antagonists, few of them are approved for clinical treatment of liver-related diseases. Developing safe and effective specific inhibitors for different HMGB1 isoforms and their interaction with receptors is the focus of future research.

Preventive and Therapeutic Effects of Crocetin in Rats with Heart Failure.

Gardenia is both a food and medicine plant. It is widely used for cardiovascular protection, and its main bioactive ingredient is crocetin. This study aims to observe the therapeutic effects of crocetin on chronic heart failure in rats induced by various etiologies. It further compares the efficacy differences between preventative and treatment administration, varying dosages, and treatment durations, to provide improved guidance for medication in heart failure rats and determine which categories of chronic heart failure rats might benefit most from crocetin. Chronic heart failure models induced by abdominal aorta constriction, renal hypertension, and coronary artery ligation were constructed. By examining cardiac function, blood biochemistry, and histopathology, the study assessed the preventive and therapeutic effects of crocetin on load-induced and myocardial ischemia-induced heart failure. The results showed that in all three models, both treatment and preventative administration of crocetin significantly improved chronic heart failure in rats, especially in preventative administration. The results indicate crocetin may be beneficial for improving symptoms and functional capacity in rats with heart failure. Furthermore, long-term administration was more effective than short-term administration across all three rat models, with therapeutic onset observed over 6 weeks.

Shape-Dependent Optical Waveguides and Low-Threshold Lasers from Polymorphic Two-Dimensional Organic Single Crystals.

Organic single crystals (OSCs) with uniform morphologies and highly ordered molecular aggregations are promising for high-performance optoelectronic devices, such as organic solid-state lasers (OSSLs), organic light-emitting transistors (OLETs), and organic light-emitting diodes (OLEDs). However, manipulating OSC morphologies and aggregation is challenging. In this study, we synthesized two-dimensional (2D) OSCs of 4,4'-bis[(N-carbazole)styryl]biphenyl (BSBCz) in hexagonal and parallelogram microplate (H-MP and P-MP) forms. Both types exhibit H-aggregation in the 2D plate plane but with different molecular transition dipole moment (TDM) orientations. This leads to different photon coupling modes with H-MP and P-MP microcavities. H-MPs enable isotropic 2D-waveguiding, forming whispering gallery mode (WGM) resonators, while P-MPs create unidirectional waveguiding, forming Fabry-Pérot mode (FP) resonators. These resonators can generate low-threshold laser emissions at 467 and 473 nm, respectively, and exhibit superior lasing stability with a half-life exceeding 2 h. Our BSBCz microplate OSCs are attractive candidates to combine controlled organic microcavities with photon transporting for realizing future integrated optoelectronic devices.

Isolation and microbial transformation of tea sapogenin from seed pomace of Camellia oleifera with anti-inflammatory effects.

In the current study, tea saponin, identified as the primary bioactive constituent in seed pomace of Camellia oleifera Abel., was meticulously extracted and hydrolyzed to yield five known sapogenins: 16-O-tiglogycamelliagnin B (a), camelliagnin A (b), 16-O-angeloybarringtogenol C (c), theasapogenol E (d), theasapogenol F (e). Subsequent biotransformation of compound a facilitated the isolation of six novel metabolites (a1-a6). The anti-inflammatory potential of these compounds was assessed using pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns molecules (DAMPs)-mediated cellular inflammation models. Notably, compounds b and a2 demonstrated significant inhibitory effects on both lipopolysaccharide (LPS) and high-mobility group box 1 (HMGB1)-induced inflammation, surpassing the efficacy of the standard anti-inflammatory agent, carbenoxolone. Conversely, compounds d, a3, and a6 selectivity targeted endogenous HMGB1-induced inflammation, showcasing a pronounced specificity. These results underscore the therapeutic promise of C. oleifera seed pomace-derived compounds as potent agents for the management of inflammatory diseases triggered by infections and tissue damage.

4'-O-MethylbavachalconeB Targeted 14-3-3ζ Blocking the Integrin ß3 Early Outside-In Signal to Inhibit Platelet Aggregation and Thrombosis.

14-3-3ζ protein, the key target in the regulation and control of integrin ß3 outside-in signaling, is an attractive new strategy to inhibit thrombosis without affecting hemostasis. In this study, 4'-O-methylbavachalconeB (4-O-MB) in Psoraleae Fructus was identified as a 14-3-3ζ ligand with antithrombosis activity by target fishing combined with ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) analysis. The competitive inhibition analysis showed that 4-O-MB targeted 14-3-3ζ and blocked the 14-3-3ζ/integrin ß3 interaction with inhibition constant (Ki) values of 9.98 ± 0.22 µM. Molecular docking and amino acid mutation experiments confirmed that 4-O-MB specifically bound to 14-3-3ζ through LSY9 and SER28 to regulate the 14-3-3ζ/integrin ß3 interaction. Besides, 4-O-MB affected the integrin ß3 early outside-in signal by inhibiting AKT and c-Src phosphorylation. Meanwhile, 4-O-MB could inhibit ADP-, collagen-, or thrombin-induced platelet aggregation function but had no effect on platelet adhesion to collagen-coated surfaces in vivo. Administration of 4-O-MB could significantly inhibit thrombosis formation without disturbing hemostasis in mice. These findings provide new prospects for the antithrombotic effects of Psoraleae Fructus and the potential application of 4-O-MB as lead compounds in the therapy of thrombosis by targeting 14-3-3ζ.

Mudanpioside C Discovered from Paeonia suffruticosa Andr. Acts as a Protein Disulfide Isomerase Inhibitor with Antithrombotic Activities.

Paeonia suffruticosa Andr. is a well-known landscape plant worldwide and also holds significant importance in China due to its medicinal and dietary properties. Previous studies have found that Cortex Moutan (CM), the dried root bark of P. suffruticosa, showed antiplatelet and cardioprotective effects, although the underlying mechanism and active compounds remain to be revealed. In this study, protein disulfide isomerase (PDI) inhibitors in CM were identified using a ligand-fishing method combined with the UHPLC-Q-TOF-MS assay. Further, their binding sites and inhibitory activities toward PDI were validated. The antiplatelet aggregation and antithrombotic activity were investigated. The results showed that two structurally similar compounds in CM were identified as the inhibitor for PDI with IC50 at 3.22 µM and 16.73 µM; among them Mudanpioside C (MC) is the most effective PDI inhibitor. Molecular docking, site-directed mutagenesis, and MST assay unequivocally demonstrated the specific binding of MC to the b'-x domain of PDI (Kd = 3.9 µM), acting as a potent PDI inhibitor by interacting with key amino acids K263, D292, and N298 within the b'-x domain. Meanwhile, MC could dose-dependently suppress collagen-induced platelet aggregation and interfere with platelet activation, adhesion, and spreading. Administration of MC can significantly inhibit thrombosis formation without disturbing hemostasis in mice. These findings present a promising perspective on the antithrombotic properties of CM and highlight the potential application of MC as lead compounds for targeting PDI in thrombosis therapy.

Oligosaccharides from Asparagus cochinchinensis for ameliorating LPS-induced acute lung injury in mice.

Asparagi radix is an edible herb with medicinal properties and is now widely used in clinical applications for improving pulmonary inflammation. However, the lung-protective effect and the active constituents of Asparagi radix are yet to be elucidated. Herein, the potential pulmonary protective effect of the oligosaccharides of Asparagi radix was investigated. We firstly identified eighteen oligosaccharides with different degrees of polymerization from Asparagi radix using HPLC-QTOF MS. Oligosaccharides were analysed for 20 samples of Asparagi radix collected from various regions in China using HILIC-ELSD and were found to stably exist in this herb. In this study, we found that AROS significantly reduced NO production and effectively down-regulated the mRNA expression of IL-6, IL-1ß and TNF-α in RAW 264.7 cells, thereby reducing the inflammatory response induced by LPS. AROS also inhibited LPS-stimulated intracellular ROS production. A murine model of lipopolysaccharide (LPS)-induced acute lung injury was used to evaluate the in vivo anti-inflammatory and lung protective efficacies of AROS. AROS ameliorated the damage to the pulmonary cellular architecture pathological injury and lung edema. AROS significantly decreased the levels of cytokines IL-6, TNF-α and IL-1ß; the levels of MPO and MDA; and superoxide dismutase consumption in vivo. This effect of oligosaccharides can explain the traditional usage of Asparagus cochinchinensis as a tonic medicine for respiratory problems, and oligosaccharides from Asparagi radix used as a natural ingredient can play an important role in protecting lung injury.

Discovering a New Drug Against Acute Kidney Injury by Using a Tailored Photoacoustic Imaging Probe.

Acute kidney injury (AKI) has become an increasing concern for patients due to the widespread clinical use of nephrotoxic drugs. Currently, the early diagnosis of AKI is still challenging and the available therapeutic drugs cannot meet the clinical demand. Herein, this work has investigated the key redox couple involved in AKI and develops a tailored photoacoustic (PA) imaging probe (AB-DiOH) which can reversibly respond to hypochlorite (ClO-)/glutathione (GSH) with high specificity and sensitivity. This probe enables the real-time monitoring of AKI by noninvasive PA imaging, with better detection sensitivity than the blood test. Furthermore, this probe is utilized for screening nephroprotective drugs among natural products. For the first time, astragalin is discovered to be a potential new drug for the treatment of AKI. After oral administration, astragalin can be efficiently absorbed by the animal body, alleviate kidney injury, and meanwhile induce no damage to other normal tissues. The treatment mechanism of astragalin has also been revealed to be the simultaneous inhibition of oxidative stress, ferroptosis, and cuproposis. The developed PA imaging probe and the discovered drug candidate provide a promising new tool and strategy for the early diagnosis and effective treatment of AKI.

A novel method for evaluating pseudoallergy based on ß-hexosaminidase and its application for traditional Chinese medicine injections.

Pseudoallergy is a typical and common adverse drug reaction to injections, especially in traditional Chinese medicine injections (TCMIs). At present, the evaluation methods for pseudoallergy include cell methods in vitro and animal methods in vivo. The mast cell evaluation method based on the ß-hexosaminidase (ß-Hex)-catalyzed substrate, 4-nitrophenyl-ß-N-acetyl-D-glucosaminide (4-NPG), is an important method for the evaluation of drug-induced pseudoallergy, but it is prone to false positive results and has insufficient sensitivity. In this study, a novel ß-Hex evaluation system with rat basophilic leukemia-2H3 cells based on high-performance liquid chromatography-fluorescence detection (HPLC-FLD) was established, which effectively increased the sensitivity and avoided false positive results. Cell viabilities were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay. In addition, a method for the determination of histamine, which is another indicator in the development of pseudoallergy, was established to validate the above method. The results of this novel method indicated that two TCMIs (Shuxuening injection and Shenqi Fuzheng injection), which were considered to be pseudoallergenic using 4-NPG, were not pseudoallergenic. Overall, the novel ß-Hex/HPLC-FLD evaluation system using Rat basophilic leukemia-2H3 cells established was effective and precise. It could be used for the evaluation of pseudoallergic reactions caused by TCMIs and other injections.

Blockade of spinal dopamine D1/D2 receptor heteromers by levo-Corydalmine suppressed calcium signaling cascade in spinal neurons to alleviate bone cancer pain in rats.

Background: Dopamine receptors have been reported to be involved in pain, while the exact effects and mechanism in bone cancer pain have not been fully explored. Methods: Bone cancer pain model was created by implanting walker 256 mammary gland carcinoma into right tibia bone cavity. Primary cultured spinal neurons were used for in vitro evaluation. FLIPR, western-blot, immunofluorescence, and Co-IP were used to detect cell signaling pathway. Results: Our results indicated that spinal dopamine D1 receptor (D1DR) and spinal dopamine D2 receptor (D2DR) could form heteromers in TCI rats, and antagonizing spinal D1DR and D2DR reduced heteromers formation and alleviated TCI-induced bone cancer pain. Further results indicated that D1DR or D2DR antagonist induced antinociception in TCI rats could be reversed by D1DR, D2DR, and D1/D2DR heteromer agonists. And Gq, IP3, and PLC inhibitors also attenuated TCI-induced bone cancer pain. In vitro results indicated that D1DR or D2DR antagonist decreased the Ca2+ oscillations upregulated by D1DR, D2DR, and D1/D2DR heteromer agonists in activated primary cultured spinal neurons. Moreover, inhibition of D1/D2DR heteromers induced antinociception in TCI rats was partially mediated by the CaMKII and MAPKs pathway. In addition, a natural compound levo-Corydalmine (l-CDL), could inhibit D1/D2DR heteromers and attenuate bone cancer pain. Results: Inhibition of spinal D1/D2DR heteromers via l-CDL decreases excitability in spinal neurons, which might present new therapeutic strategy for bone cancer pain.

Quantifying Impairment and Disease Severity Using AI Models Trained on Healthy Subjects.

Automatic assessment of impairment and disease severity is a key challenge in data-driven medicine. We propose a novel framework to address this challenge, which leverages AI models trained exclusively on healthy individuals. The COnfidence-Based chaRacterization of Anomalies (COBRA) score exploits the decrease in confidence of these models when presented with impaired or diseased patients to quantify their deviation from the healthy population. We applied the COBRA score to address a key limitation of current clinical evaluation of upper-body impairment in stroke patients. The gold-standard Fugl-Meyer Assessment (FMA) requires in-person administration by a trained assessor for 30-45 minutes, which restricts monitoring frequency and precludes physicians from adapting rehabilitation protocols to the progress of each patient. The COBRA score, computed automatically in under one minute, is shown to be strongly correlated with the FMA on an independent test cohort for two different data modalities: wearable sensors ($\rho = 0.845$, 95% CI [0.743,0.908]) and video ($\rho = 0.746$, 95% C.I [0.594, 0.847]). To demonstrate the generalizability of the approach to other conditions, the COBRA score was also applied to quantify severity of knee osteoarthritis from magnetic-resonance imaging scans, again achieving significant correlation with an independent clinical assessment ($\rho = 0.644$, 95% C.I [0.585,0.696]).

Gender differences in depressive symptoms among Chinese older adults based on fairlie decomposition analysis.

This study aimed to investigate the factors influencing depressive symptoms among Chinese older adults based on gender differences. Data from the eighth wave of Chinese Longitudinal Health Longevity Survey were used. We analyzed the influencing factors of depressive symptoms reported by older adults using the chi-squared test and logistic model. Fairlie decomposition analysis was performed to quantify the contribution level of each influencing factor. We found that 11.71 % of older adults met the CES-D-10 criteria for depressive symptoms. Females (13.89 %) reported a significantly higher level of depressive symptoms than males (9.24 %). Age, residence, sleeping time, exercise, activities of daily living functional disability, instrumental activity of daily living functional disability, and living status influenced depressive symptoms in older adults. Higher education and lower body mass index were only significant in male, whereas middle annual income and exercising were significant only in female. The Fairlie decomposition model explained the reasons for 75.64 % of the gender differences in depressive symptoms, with instrumental activity of daily living functional disability (33.60 %), age (-17.79 %), and education level (17.41 %) being major factors affecting gender differences in depressive symptoms. This is the first nationwide study to examine gender differences in depressive symptoms among older adults. These results provide a basis for relevant Chinese government departments to formulate policies to prevent and control depressive symptoms.

Rapid screening and identification of superoxide dismutase activators from traditional Chinese medicines based on affinity ultrafiltration mass chromatography combined with molecular docking.

In the present study, a comprehensive strategy integrating affinity ultrafiltration high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UF-HPLC-Q-TOF-MS), in silico molecular docking and bioassays was established to rapidly screen natural SOD activators from traditional Chinese medicines. As illustrative case studies, Schisandra chinensis, Fructus cnidii and Radix ophiopogonis were chosen to develop and verify the strategy. The HPLC-Q-TOF-MS was used to identify the compounds in comparison with reference standards and literature data. A total of eight compounds, including four biphenyl-cyclooctene ligands from Schisandra chinensis and four coumarins from Fructus cnidii, were found to potentially increase SOD activities. No ligands were found in the extract of Radix ophiopogonis. Then, in silico molecular docking was performed to investigate the binding site and binding affinity of the candidates on SOD. Compared to the nonspecific ligands screened from the extract, the specific ligands presented stronger binding affinities. In addition, the activity and kinetic parameters of the SOD-ligand were investigated through an improved pyrogallol autoxidation method. Gomisin J and xanthotoxin showed a stronger ability to increase SOD activities. The present study indicated that combining UF-HPLC-Q-TOF-MS and in silico molecular docking offers a powerful and meaningful tool to rapidly screen SOD activators from traditional Chinese medicines.

Decomposition and comparative analysis of health inequities between the male and female older adults in China: a national cross-sectional study.

BACKGROUND: This study aimed to examine the factors influencing self-rated health (SRH) among Chinese older adults by gender differences and provide suggestions and theoretical references to help make policies for older adults' health concerns by government agencies. METHODS: Chinese Longitudinal Health Longevity Survey (CLHLS) in 2018 was adopted, the chi-squared test and the logistic regression analysis were performed to analyse self-rated health reported by Chinese female and male older adults and its influencing factors. In addition, Fairlie decomposition analysis was performed to quantify the contribution level of different influencing factors. RESULTS: Among older adults, males (48.0%) reported a significantly higher level of good self-rated health than females (42.3%). Residence, body mass index (BMI), self-reported income, smoking, drinking, exercise, and social activity were the factors that influenced SRH reported by male and female respondents, with age, marital status and education reaching the significance level only in women. The Fairlie decomposition model can explain the underlying reasons for 86.7% of the gender differences in SRH, with self-reported income (15.3%), smoking (32.7%), drinking (42.5%), exercise (17.4%), social activity (15.1%) and education (-14.6%) being the major factors affecting gender differences in SRH. CONCLUSIONS: The study results can help promote the implementation of the Healthy China Initiative, inform intervention measures, and offer new proposals on creating policies for older adults' health issues by the Chinese government to improve health equity.

Illumination of Hydroxyl Radical in Kidney Injury and High-Throughput Screening of Natural Protectants Using a Fluorescent/Photoacoustic Probe.

The hydroxyl radical (•OH) is shown to play a crucial role in the occurrence and progression of acute kidney injury (AKI). Therefore, the development of a robust •OH probe holds great promise for the early diagnosis of AKI, high-throughput screening (HTS) of natural protectants, and elucidating the molecular mechanism of intervention in AKI. Herein, the design and synthesis of an activatable fluorescent/photoacoustic (PA) probe (CDIA) for sensitive and selective imaging of •OH in AKI is reported. CDIA has near-infrared fluorescence/PA channels and fast activation kinetics, enabling the detection of the onset of •OH in an AKI model. The positive detection time of 12 h using this probe is superior to the 48-hour detection time for typical clinical assays, such as blood urea nitrogen and serum creatinine detection. Furthermore, a method is established using CDIA for HTS of natural •OH inhibitors from herbal medicines. Puerarin is screened out by activating the Sirt1/Nrf2/Keap1 signaling pathway to protect renal cells in AKI. Overall, this work provides a versatile and dual-mode tool for illuminating the •OH-related pathological process in AKI and screening additional compounds to prevent and treat AKI.

Background and roles: myosin in autoimmune diseases.

The myosin superfamily is a group of molecular motors. Autoimmune diseases are characterized by dysregulation or deficiency of the immune tolerance mechanism, resulting in an immune response to the human body itself. The link between myosin and autoimmune diseases is much more complex than scientists had hoped. Myosin itself immunization can induce experimental autoimmune diseases of animals, and myosins were abnormally expressed in a number of autoimmune diseases. Additionally, myosin takes part in the pathological process of multiple sclerosis, Alzheimer's disease, Parkinson's disease, autoimmune myocarditis, myositis, hemopathy, inclusion body diseases, etc. However, research on myosin and its involvement in the occurrence and development of diseases is still in its infancy, and the underlying pathological mechanisms are not well understood. We can reasonably predict that myosin might play a role in new treatments of autoimmune diseases.