Chiral Bisphosphine-Catalyzed Asymmetric Staudinger/aza-Wittig Reaction: An Enantioselective Desymmetrizing Approach to Crinine-Type Amaryllidaceae Alkaloids.

An unprecedented chiral bisphosphine-catalyzed asymmetric Staudinger/aza-Wittig reaction of 2,2-disubstituted cyclohexane-1,3-diones is reported, enabling the facile access of a broad range of cis-3a-arylhydroindoles in high yields with excellent enantioselectivities. The key to the success of this work relies on the first application of chiral bisphosphine DuanPhos to the asymmetric Staudinger/aza-Wittig reaction. An effective reductive system has been established to address the challenging PV═O/PIII redox cycle associated with the chiral bisphosphine catalyst. In addition, comprehensive experimental and computational investigations were carried out to elucidate the mechanism of the asymmetric reaction. Leveraging the newly developed chemistry, the enantioselective total syntheses of several crinine-type Amaryllidaceae alkaloids, including (+)-powelline, (+)-buphanamine, (+)-vittatine, and (+)-crinane, have been accomplished with remarkable conciseness and efficiency.

The effects of hyaluronan and proteoglycan link protein 1 (HAPLN1) in ameliorating spinal cord injury mediated by Nrf2.

Excessive inflammatory response and oxidative stress (OS) play an important role in the pathogenesis of spinal cord injury (SCI). Balance of inflammation and prevention of OS have been considered an effective strategy for the treatment of SCI. Hyaluronan and proteoglycan link protein 1 (HAPLN1), also known as cartilage link protein, has displayed a wide range of biological and physiological functions in different types of tissues and cells. However, whether HAPLN1 regulates inflammation and OS during SCI is unknown. Therefore, we aimed to examine whether HAPLN1 can have a protective effect on SCI. In this study, both in vitro and in vivo SCI models were established. Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining assays were used. Western blotting and enzyme-linked immunosorbent assay were employed to assess the expression of proteins. Our results demonstrate that the administration of HAPLN1 promoted the recovery of motor neurons after SCI by increasing the Basso mouse scale score, increasing the numbers of motor neurons, and preventing apoptosis of spinal cord cells. Additionally, HAPLN1 mitigated OS in spinal cord tissue after SCI by increasing the content of superoxide dismutase SOD and the activity of glutathione peroxidase but reducing the levels of malondialdehyde. Importantly, we found that HAPLN1 stimulated the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and stimulated the expression of heme oxygenase-1 and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase-1, which mediated the attenuation of HAPLN1 in activation of the NOD-like receptor protein 3 (NLRP3) inflammasome by reducing the levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin-1ß. Correspondingly, in vitro experiments show that the presence of HAPLN1 suppressed the NLRP3 inflammasome and prevented cell injury against H2O2 in PC12 cells. These effects were mediated by the Nrf2/ARE pathway, and inhibition of Nrf2 with ML385 abolished the beneficial effects of HAPLN1. Based on these findings, we conclude that HAPLN1 inhibits the NLRP3 inflammasome through the stimulation of the Nrf2/ARE pathway, thereby suppressing neuroinflammation, enhancing motor neuronal survival, and improving the recovery of nerve function after SCI.

Total Synthesis of Carolacton and Demethylcarolactons with Potent Antiviral Activity.

Carolacton, a naturally occurring MTHFD1 inhibitor, exhibits potent inhibitory activity against various RNA viruses including SARS-CoV-2. Herein, we present a concise total synthesis of carolacton, featuring the Krische allylation, Marshall coupling, NHK coupling, and RCM reaction as key elements. Additionally, we have synthesized three simplified carolacton analogues, one of which, namely, 14-demethyl-carolacton, exhibited notable antiviral activity. The present work paves the way for further exploration of the therapeutic potential of carolacton and its analogues.

Correlation between functional drainage and survival in malignant biliary obstruction after percutaneous biliary drainage.

Purpose: Malignant biliary obstruction (MBO) is common in patients with advanced malignant tumors, leading to poor prognosis and hindering antitumor therapy. The purpose of our study was to assess the survival outcomes for patients under therapy after percutaneous transhepatic biliary drainage (PTBD) and identify prognostic factors associated with survival in patients with MBO. Methods: From July 2010 to February 2021, 269 patients with MBO secondary to malignant tumor were divided into two groups (functional success and non-functional success). Survival time and prognostic factors were analyzed by Kaplan-Meier curves and the Cox model. Results: The overall median survival time after PTBD was 4.6 months (95 % IC:3.9-5.3). The 3- and 6-month survival rates were 68.0 % and 38.7 %, respectively. The median survival improved from 3.2 months to 8.4 months when the procedure achieved functional success. Multivariate analysis demonstrated that functionally successful drainage and antitumor treatment after PTBD were independent positive prognostic factors, but the total bilirubin after drainage and tumor size were independent negative predictive values. Conclusions: Functionally successful drainage could prolong survival time in patients with malignant biliary obstruction. Palliative care after drainage can prolong patient survival and improve their quality of life.

Hydrogen gas alleviates acute ethanol-induced hepatotoxicity in mice via modulating TLR4/9 innate immune signaling and pyroptosis.

Alcoholic liver disease (ALD), which is induced by chronic heavy alcohol consumption, accompanies complicated pathological mechanisms, including oxidative stress, inflammation, cell death, epigenetic changes and acetaldehyde-mediated toxicity. Hydrogen (H2) is the lightest gas with multiple biological effects such as high selective anti-oxidation, anti-inflammation and anti-apoptosis. However, the dose effects and innate immune mechanisms of intraperitoneal injection of H2 on ALD are limited. Here, we used acute ethanol-induced hepatotoxicity mice models to estimate the actions of intraperitoneal injection of H2 on ALD. The effects of H2 on acute ethanol-induced liver damage were examined by hepatic oil red O staining, quantitative PCR (qPCR) for lipid metabolic genes, hepatic triglyceride (TG) and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Hepatic mitochondrial superoxide (MitoSOX), 3-nitrotyrosine (3-NT), malondialdehyde (MDA), and glutathione (GSH) levels were examined to evaluate oxidative stress. Immunoblot, and immunofluorescence staining were used to further confirm the innate immune molecular targets of H2. Our results showed that intraperitoneal injection of H2 improved acute ethanol-induced liver injury in mice in a dose dependent manner, as indicated by decreasing serum ALT and AST levels, hepatic TG levels, and increasing lipid export genes (Mttp and Apob) mRNA levels and reducing fatty acid uptake gene (CD36) mRNA levels. Mechanistically, H2 inhibited hepatic oxidative stress as indicated by reducing reactive oxygen species (ROS), 3-NT, and MDA levels in the liver, while increasing hepatic GSH levels; inhibited the overactived TLR4/9-NF-κB-TNF-α/IL-1ß/IL-18 innate immune signaling; suppressed the canonical Caspase-1-GSDMD pyroptosis signaling, and the non-canonical pyroptosis signaling, such as Caspase-11-GSDMD, Caspase-8-GSDMD and Caspase-3-GSDME signaling. Therefore, our study highlights that intraperitoneal injection of H2 may represent a novel therapeutic and safe strategy for ALD via modulating oxidative stress, innate immunity and pyroptosis.

Detection of copy number variations based on a local distance using next-generation sequencing data.

As one of the main types of structural variation in the human genome, copy number variation (CNV) plays an important role in the occurrence and development of human cancers. Next-generation sequencing (NGS) technology can provide base-level resolution, which provides favorable conditions for the accurate detection of CNVs. However, it is still a very challenging task to accurately detect CNVs from cancer samples with different purity and low sequencing coverage. Local distance-based CNV detection (LDCNV), an innovative computational approach to predict CNVs using NGS data, is proposed in this work. LDCNV calculates the average distance between each read depth (RD) and its k nearest neighbors (KNNs) to define the distance of KNNs of each RD, and the average distance between the KNNs for each RD to define their internal distance. Based on the above definitions, a local distance score is constructed using the ratio between the distance of KNNs and the internal distance of KNNs for each RD. The local distance scores are used to fit a normal distribution to evaluate the significance level of each RDS, and then use the hypothesis test method to predict the CNVs. The performance of the proposed method is verified with simulated and real data and compared with several popular methods. The experimental results show that the proposed method is superior to various other techniques. Therefore, the proposed method can be helpful for cancer diagnosis and targeted drug development.

Yao-Shan of traditional Chinese medicine: an old story for metabolic health.

Type 2 diabetes mellitus, nonalcoholic fatty liver disease (NAFLD), cardio-cerebrovascular diseases (CCVDs), hyperuricemia and gout, and metabolic-related sexual dysfunction are metabolic diseases that affect human health in modern society. Scientists have made great efforts to investigate metabolic diseases using cell models in vitro or animal models in the past. However, the findings from cells or animals are difficult to translate into clinical applications due to factors such as the in vitro and in vivo differences; the differences in anatomy, physiology, and genetics between humans and animals; and the differences in microbiome-host interaction. The Chinese have extensively used the medicated diet of traditional Chinese medicine (TCM) (also named as Yao-Shan of TCM, Chinese Yao-Shan et al.) to maintain or improve cardiometabolic health for more than 2,200 years. These ancient classic diets of TCM are essential summaries of long-term life and clinical practices. Over the past 5 years, our group has made every effort to collect and sort out the classic Yao-Shan of TCM from the ancient TCM literature since Spring and Autumn and Warring States Period, especially these are involved in the prevention and treatment of metabolic diseases, such as diabetes, NAFLD, CCVDs, hyperuricemia and gout, and sexual dysfunction. Here, we summarized and discussed the classic Yao-Shan of TCM for metabolic diseases according to the time recorded in the ancient literature, and revised the Latin names of the raw materials in these Yao-Shan of TCM. Moreover, the modern medicine evidences of some Yao-Shan of TCM on metabolic diseases have also been summarized and emphasized in here. However, the exact composition (in terms of ratios), preparation process, and dosage of many Yao-Shan are not standardized, and their main active ingredients are vague. Uncovering the mystery of Yao-Shan of TCM through modern biological and chemical strategies will help us open a door, which is ancient but now looks new, to modulate metabolic homeostasis and diseases.

The renal artery-aorta angle associated with renal artery plaque: a retrospective analysis based on CT.

PURPOSE: To investigate the relationship between renal artery anatomical configuration and renal artery plaque (RAP) based on 320-row CT. METHODS: The abdominal contrast-enhanced CT data from 210 patients was retrospectively analyzed. Among 210 patients, there were 118 patients with RAP and 92 patients with no RAP. The anatomical parameters between lesion group and control group were compared and analyzed by using t-test, χ2-test and logistic regression analysis. RESULTS: (1) There were statistical differences on age, hypertension, diabetes, hypertriglyceridemia and hypercholesterolemia between lesion group and control group. (2) The differences on the distribution and type and of RAP between lesion group and control group were statistically significant. The most common position was the proximal, and the most common type was calcified plaque. (3)There were significant statistical differences on the proximal diameter of renal artery and renal artery-aorta angle A between lesion group and control group. The differences on the other anatomical factors between two groups were not statistically significant. (4) The result of logistic regression analysis showed that right RAP was related to age, hypertension and right renal artery angle A (the AUC of ROC = 0.82), and left RAP was related to high serum cholesterol, age and left renal artery angle A(the AUC of ROC = 0.83). (5) The RAP was associated with renal artery-aorta angle A, but the differences on distribution, type stability of RAP between R1 (L1) group and R2 (L2) group were not statistically significant. CONCLUSIONS: The RAP was associated with age, hypertension, hypercholesterolemia and renal artery-aorta angle A. Adults which had the greater renal artery-aorta angle A and the other above risk factors may be at increased risk for RAP.

An ultra-sensitive and selective electrochemical sensor based on GOCS composite and ion imprinted polymer for the rapid detection of Cd2+ in food samples.

An ultra-sensitive and selective electrochemical sensor was proposed through the combination of carbon disulfide-functionalized graphene oxide (GOCS) composite with high conductivity and cadmium ion-imprinted polymer (IIP). Using pyrrole as the functional monomer and Cd2+ as the template ion, the IIP was formed by in situ electropolymerization on GOCS composite. Under the optimized experimental conditions, the sensor exhibited a good linear relationship in the range of 0.5-50 µg/L Cd2+ concentration, with the lowest detection limit of 0.23 µg/L. The sensor exhibited not only good selectivity for the determination of Cd2+, but also good repeatability with current response remaining 87.6 % after four cycles. Furthermore, the sensor exhibited similar sensing performance in lettuce, orange and peach with recovery ranging from 82.6 % to 110.63 %. This work is expected to provide an electrochemical sensor with excellent selectivity, good stability and sensitivity for the detection of trace amounts of Cd2+ in real samples.

Subtraction Improves the Accuracy of Coronary CT Angiography in Patients with Severe Calcifications in Identifying Moderate and Severe Stenosis: A Multicenter Study.

RATIONALE AND OBJECTIVES: To investigate the diagnostic accuracy of subtraction coronary computed tomographic angiography (CCTAsub) in identifying ≥ 50% and ≥ 70% coronary stenosis in patients with different degrees of calcification. MATERIALS AND METHODS: In this study, 180 patients with coronary calcified plaques who underwent both coronary CT angiography and invasive coronary angiography (ICA) were prospectively enrolled at five centers. Patients were divided into three groups according to the Agatston score: group A (low to moderate, < 400), group B (high, 400-999), and group C (very high, ≥ 1000). Diagnostic accuracies estimated by area under the receiver operating characteristic curve (AUC) were compared between conventional CCTA (CCTAcon) and CCTAsub, with ICA as a reference standard. RESULTS: There were 86 patients in group A, 44 in group B, and 50 in group C. In identifying ≥ 70% coronary stenosis, subtraction improved the diagnostic accuracies on a per-segment basis in group B (AUC: 0.80 vs 0.92, p = 0.001) and group C (AUC: 0.75 vs 0.84, p = 0.001) after subtraction. When identifying ≥ 50% coronary stenosis, the per-segment AUC of CCTAsub in group B and C were significantly higher than that in CCTAcon (group B: 0.81 vs 0.92, p < 0.001; group C: 0.77 vs 0.88, p < 0.001). However, no improvement was observed in group A. CONCLUSION: Subtraction achieved better diagnostic accuracy in patients with Agatston score ≥ 400, both in identifying ≥ 50% and ≥ 70% coronary stenosis, which was instructive for the application of subtraction in clinical practice.

Effects of variety and origin on the metabolic and texture characteristics of quinoa seeds based on ultrahigh-performance liquid chromatography coupled with high-field quadrupole-orbitrap high-resolution mass spectrometry.

The nutrition and functionality of Chenopodium quinoa Willd are closely related to its components; however, these properties vary widely in different varieties of C. quinoa Willd from different origins. Using ultrahigh-performance liquid chromatography coupled with high-field quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-QE HF HRMS) for metabolomics analysis, we performed nontargeted metabolomics analysis of C. quinoa Willd of different color varieties and origins and evaluated the texture characteristics after cooking. Both the variety and origin significantly affected the metabolic characteristics of C. quinoa Willd. The differences in the composition and texture properties were closely related to the lipid, amino acid, and polyphenol contents. The contents of kaempferol, catechol, myricetin 7-(6'-galloside), tyrosine, prostaglandin I2, and glutathione in white, red, and black quinoa significantly differed, and the variety had a greater effect on the lipid content than on the polyphenol and amino acid contents. At the same processing level, the texture properties of white and red quinoa were better than those of black quinoa. Furthermore, the contents of differential polyphenols and amino acids in Gansu white quinoa were higher than those in quinoa from the other three producing areas. The contents of differential polyphenols and terpenoids in Inner Mongolia white quinoa were relatively low, whereas in Shanxi white quinoa, the contents of differential amino acids were relatively low and those of differential terpenoids were relatively high. The levels of quercetin and its derivatives, kaempferol and its derivatives, 9-HODE, azelaic acid, sebacic acid, elaidic acid, linoleic acid, prostaglandin H2, glutathione, 5-aminovaleric acid, and other compounds significantly differed in quinoa from different origins; thus, these compounds can be used as metabolic markers to identify the origin of quinoa. The texture properties of white quinoa from Qinghai and Inner Mongolia were better than those of white quinoa from Gansu and Shanxi. Although C. quinoa Willd can tolerate harsh environments, its grain quality varies widely. Cultivating C. quinoa Willd varieties according to local conditions is important for improving their yield and quality.

Aqueous phase synthesis of ion-imprinted cryogel for paper-based colorimetric detection of As(V) with high selectivity.

A novel hydrophilic As(V) ion-imprinted cryogel (IIC) was green prepared by cryogelation in aqueous environment which was coincident with the adsorption condition and can improve the specific recognition performance. The methacrylamido propyl trimethyl ammonium chloride (MPTAC) was selected as the functional monomer and the saturated adsorption capacity of the prepared IIC and NIC were 55.0 mg/g and 29.4 mg/g, and with high imprinting factor of 1.87. Additionally, the prepared IIC showed admirable reusability and high selectivity, and the recovery was in the range 81.2-97.9% with RSD range of 1.9-4.3%, which was similar to the value obtained by hydride generation atomic absorption spectrometry. IIC can be used as solid material for colorimetric detection at the ultraviolet wavelength of 858 nm without color interference of material matrix, in the range 5-200 µg/L (R2 = 0.990) with a detection limit of 0.970 µg/L. Obviously, this synthetic strategy provides a simple, efficient, and green method for the preparation of water-compatible ion-imprinted polymers providing selective separation and detection of trace As(V) in real complex samples.

Early intervention with acupuncture improves the outcome of patients with Bell's palsy: A propensity score-matching analysis.

Objective: Although acupuncture is widely used as a complementary therapy in the treatment of Bell's palsy (BP) when to initiate acupuncture is still controversial. This study aims to determine the efficacy of the early intervention by acupuncture on BP. Methods: We retrospectively gathered clinical data from the Third Affiliated Hospital of SUN-YAT SEN University between 2016 and 2021. We selected newly diagnosed patients with BP who were diagnosed by registered neurologists or acupuncturists formally. The qualified patients were divided into two groups according to whether or not initial acupuncture treatment was given within 7 days from the onset of palsy. Cohorts were balanced using 1:1 propensity score matching (PSM). Cox proportional hazards modeling and Kaplan-Meier analysis were applied to determine the differences between the two groups. The outcome included time to complete recovery of facial function, the rate of complete recovery, and the occurrence of sequelae in 24 weeks. Results: A total of 345 patients were eligible for this study and were divided into the manual acupuncture/electroacupuncture (MA/EA) group (n = 76) and the EA group (n = 125). In the propensity score-matched cohort, the time to complete recovery was significantly shorter in the MA/EA group compared with the patients in the EA group (hazard ratio 1.505, 95% CI 1.028-2.404, p <0.05). The MA/EA group had a higher rate of favorable outcomes at 12 weeks than the EA group (93.4 vs. 80.3%, p = 0.032), and the occurrence of sequelae at 24 weeks showed a greater reducing trend in the MA/EA group than the EA group (6.6 vs. 16.4%, p = 0.088). Conclusion: Acupuncture intervention at the acute stage of BP could shorten the time to recovery and improve the outcome. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR 2200058060.

Effect of Thermal Processing on the Metabolic Components of Black Beans on Ultra-High-Performance Liquid Chromatography Coupled with High-Field Quadrupole-Orbitrap High-Resolution Mass Spectrometry.

An ultra-high-performance liquid chromatography coupled with high-field quadrupole-orbitrap mass spectrometry (UHPLC-QE-MS) histological platform was used to analyze the effects of two thermal processing methods (cooking and steaming) on the nutritional metabolic components of black beans. Black beans had the most amino acids, followed by lipids and polyphenols, and more sugars. Multivariate statistical analysis indicated that heat processing significantly affected the metabolic component content in black beans, with effects varying among different components. Polyphenols, especially flavonoids and isoflavones, were highly susceptible. A total of 197 and 210 differential metabolites were identified in both raw black beans and cooked and steamed black beans, respectively. Cooking reduced the cumulative content of amino acids, lipids, polyphenols, sugars, and nucleosides, whereas steaming reduced amino acid and lipid content, slightly increased polyphenol content, and significantly increased sugar and nucleoside content. Our results indicated that metabolic components were better retained during steaming than cooking. Heat treatment had the greatest impact on amino acids, followed by polyphenols, fatty acids, sugars, and vitamins, indicating that cooking promotes the transformation of most substances and the synthesis of a few. The results of this study provide a basis for further research and development of nutritional products using black beans.

Noble Gases Therapy in Cardiocerebrovascular Diseases: The Novel Stars?

Cardiocerebrovascular diseases (CCVDs) are the leading cause of death worldwide; therefore, to deeply explore the pathogenesis of CCVDs and to find the cheap and efficient strategies to prevent and treat CCVDs, these are of great clinical and social significance. The discovery of nitric oxide (NO), as one of the endothelium-derived relaxing factors and its successful utilization in clinical practice for CCVDs, provides new ideas for us to develop drugs for CCVDs: "gas medicine" or "medical gases." The endogenous gas molecules such as carbon monoxide (CO), hydrogen sulfide (H2S), sulfur dioxide (SO2), methane (CH4), and hydrogen (H2) have essential biological effects on modulating cardiocerebrovascular homeostasis and CCVDs. Moreover, it has been shown that noble gas atoms such as helium (He), neon (Ne), argon (Ar), krypton (Kr), and xenon (Xe) display strong cytoprotective effects and therefore, act as the exogenous pharmacologic preventive and therapeutic agents for CCVDs. Mechanistically, besides the competitive inhibition of N-methyl-D-aspartate (NMDA) receptor in nervous system by xenon, the key and common mechanisms of noble gases are involved in modulation of cell death and inflammatory or immune signals. Moreover, gases interaction and reduction in oxidative stress are emerging as the novel biological mechanisms of noble gases. Therefore, to investigate the precise actions of noble gases on redox signals, gases interaction, different cell death forms, and the emerging field of gasoimmunology, which focus on the effects of gas atoms/molecules on innate immune signaling or immune cells under both the homeostatic and perturbed conditions, these will help us to uncover the mystery of noble gases in modulating CCVDs.

Efficacy and safety of AnluoHuaxian pills on chronic hepatitis B with normal or minimally elevated alanine transaminase and early liver fibrosis: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). AIM OF THE STUDY: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. RESULTS: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. CONCLUSIONS: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.

A shortest path-based approach for copy number variation detection from next-generation sequencing data.

Copy number variation (CNV) is one of the main structural variations in the human genome and accounts for a considerable proportion of variations. As CNVs can directly or indirectly cause cancer, mental illness, and genetic disease in humans, their effective detection in humans is of great interest in the fields of oncogene discovery, clinical decision-making, bioinformatics, and drug discovery. The advent of next-generation sequencing data makes CNV detection possible, and a large number of CNV detection tools are based on next-generation sequencing data. Due to the complexity (e.g., bias, noise, alignment errors) of next-generation sequencing data and CNV structures, the accuracy of existing methods in detecting CNVs remains low. In this work, we design a new CNV detection approach, called shortest path-based Copy number variation (SPCNV), to improve the detection accuracy of CNVs. SPCNV calculates the k nearest neighbors of each read depth and defines the shortest path, shortest path relation, and shortest path cost sets based on which further calculates the mean shortest path cost of each read depth and its k nearest neighbors. We utilize the ratio between the mean shortest path cost for each read depth and the mean of the mean shortest path cost of its k nearest neighbors to construct a relative shortest path score formula that is able to determine a score for each read depth. Based on the score profile, a boxplot is then applied to predict CNVs. The performance of the proposed method is verified by simulation data experiments and compared against several popular methods of the same type. Experimental results show that the proposed method achieves the best balance between recall and precision in each set of simulated samples. To further verify the performance of the proposed method in real application scenarios, we then select real sample data from the 1,000 Genomes Project to conduct experiments. The proposed method achieves the best F1-scores in almost all samples. Therefore, the proposed method can be used as a more reliable tool for the routine detection of CNVs.

Screening of heat stress-regulating active fractions in mung beans.

Introduction: Heat stress caused by high temperatures has important adverse effects on the safety and health status of humans and animals, and dietary interventions to alleviate heat stress in daily life are highly feasible. Methods: In this study, the components of mung bean that have heat stress-regulating effects were characterized by in vitro antioxidant indicators and heat stress cell models. Results: As a result, 15 target monomeric polyphenol fractions were identified based on untargeted analysis on an ultra performance liquid chromatography coupled with high field quadrupole orbit high resolution mass spectrometry (UHPLC-QE-HF-HRMS) platform and available reports. The results of DPPH and ABTS radical scavenging showed that mung bean polyphenols (crude extract) and 15 monomeric polyphenols had better antioxidant activity, followed by oil and mung bean peptides, while protein and polysaccharides had relatively poor antioxidant activity. Qualitative and quantitative assays for 20 polyphenols (15 polyphenols and 5 isomers) were then established based on platform targets. Vitexin, orientin, and caffeic acid were identified as monomeric polyphenols for heat stress control in mung beans based on their content. Finally, mild (39°C), moderate (41°C), and severe (43°C) heat stress models were successfully constructed based on mouse intestinal epithelial Mode-k cells and human colorectal adenocarcinoma Caco-2 cell lines, all with an optimal heat stress modeling time of 6 h. Screening of mung bean fractions using HSP70 mRNA content, a key indicator of heat stress. As a result, HSP70 mRNA content was significantly up-regulated by different levels of heat stress in both cell models. The addition of mung bean polyphenols (crude extract), vitexin, orientin, and caffeic acid resulted in significant down-regulation of HSP70 mRNA content, and the higher the level of heat stress, the more significant the regulation effect, with orientin having the best effect. Mung bean proteins, peptides, polysaccharides, oils and mung bean soup resulted in increased or no change in HSP70 mRNA levels after most heat stresses. Discussion: The polyphenols were shown to be the main heat stress regulating components in mung bean. The results of the validation experiments confirm that the above three monomeric polyphenols may be the main heat stress regulating substances in mung bean. The role of polyphenols in the regulation of heat stress is closely linked to their antioxidant properties.

Chemical trigger-enabled bioconjugation reaction.

Development of conceptually novel and practically useful bioconjugation reactions has been an intense pursuit of chemical biology research. Herein, we report an unprecedented bioconjugation reaction that hinges on a chemical trigger-enabled inverse-electron-demand Diels-Alder (IEDDA) cycloaddition of trans-cycloheptene (TCH) with tetrazine. Unlike the conventional strain-promoted bioconjugation reactions that utilize built-in strained alkenes as reactants, the current one features a "trigger-release-conjugate" reaction model, in which a highly strained TCH species is released from a bench-stable bicyclic N-nitrosourea (BNU) derivative upon treatment with an external stimulus. It is noteworthy that the reactivity-stability balance of BNU derivatives could be tuned by manipulating their N-1 substituents. As a proof-of-concept case, this new chemical trigger-enabled IEDDA reaction has been applied to in vitro protein labeling and pretargeted cell imaging. This work opens a new avenue to utilize BNU derivatives as a new class of chemical reporters in bioconjugate chemistry.