Development and Application of Real-Time PCR Assay for Detection of Salmonella Abortusequi.

Salmonella enterica subsp. enterica serovar Abortusequi is a major pathogen in horse and donkey herds, causing abortion in pregnant equids and resulting in enormous economic losses. A rapid and reliable method is urgently needed to detect S. Abortusequi in herds where the disease is suspected. To achieve this goal, a TaqMan-based real-time PCR assay targeting the gene for the flagellin protein phase 2 antigen FljB was developed. This real-time PCR assay had high specificity, sensitivity, and reproducibility. The detection limit of the assay was 30 copies/µL of standard plasmid and 10 CFU/µL of bacterial DNA. Furthermore, 540 clinical samples, including 162 tissue, 192 plasma, and 186 vaginal swab samples collected between 2018 and 2021 in China, were tested to assess the performance of the developed assay. Compared to the gold standard method of bacterial isolation, the real-time PCR assay exhibited 100% positive agreement for all tissue, plasma and vaginal swab tests. Additionally, this assay detected DNA from S. Abortusequi from 56.7% (34/60) culture-negative tissue and 22.9% (41/179) culture-negative vaginal swab samples from infected equids. Receiver operating characteristic analysis demonstrated that the results of the developed real-time PCR assays were in significant agreement with those of the culture method. The real-time PCR assay can be completed within 45 min of extraction of DNA from samples. Our results show that this assay could serve as a reliable tool for the rapid detection of S. Abortusequi in tissue, plasma, and vaginal swab clinical samples.

Advanced Composites Inspired by Biological Structures and Functions in Nature: Architecture Design, Strengthening Mechanisms, and Mechanical-Functional Responses.

The natural design and coupling of biological structures are the root of realizing the high strength, toughness, and unique functional properties of biomaterials. Advanced architecture design is applied to many materials, including metal materials, inorganic nonmetallic materials, polymer materials, and so on. To improve the performance of advanced materials, the designed architecture can be enhanced by bionics of biological structure, optimization of structural parameters, and coupling of multiple types of structures. Herein, the progress of structural materials is reviewed, the strengthening mechanisms of different types of structures are highlighted, and the impact of architecture design on the performance of advanced materials is discussed. Architecture design can improve the properties of materials at the micro level, such as mechanical, electrical, and thermal conductivity. The synergistic effect of structure makes traditional materials move toward advanced functional materials, thus enriching the macroproperties of materials. Finally, the challenges and opportunities of structural innovation of advanced materials in improving material properties are discussed.

Exploring the binding characteristics of bovine serum albumin with tyrosine kinase inhibitor entrectinib: Multi-spectral analysis and theoretical calculation.

Entrectinib (ENB) is one of multi-target tyrosine kinase inhibitors, which is mainly used for treating neurotrophic tyrosine receptor kinase gene fusion positive solid tumors. The binding characteristics of ENB and bovine serum albumin (BSA) were studied by experiments and theoretical calculations. The steady-state fluorescence showed that ENB quenched the fluorescence of BSA through mixed quenching, and ENB was dominated by static quenching at low concentration. ENB and BSA had a moderate affinity, formed a complex with a stoichiometric ratio of 1:1 and the binding constant of about 105 M-1 at 298 K, and Förster non-radiative energy transfer occurs. According to the driving force competition experiment, thermodynamic parameter analysis and theoretical calculation, hydrogen bond, van der Waals force and hydrophobic force were the main factors affecting the stability of the ENB-BSA complex. Molecular docking and site markers competition showed that ENB spontaneously bound to the Site III of BSA so that ENB could make the skeleton of BSA loose, the spatial structure of BSA changed (α-helix decreased by 3.1%, random coil increased by 1.7%), and the microenvironment of Tyr and Trp residues changed. The existence of Co2+ metal ions can enhance the binding effect, thus prolonging the half-life of ENB in vivo, which may improve the efficacy of ENB, while Ca2+, Cu2+ and Mg2+ metal ions will reduce the efficacy of ENB.

Effect of fermentation on structural properties and antioxidant activity of wheat gluten by Bacillus subtilis.

Bacillus subtilis has been extensively studied for its ability to inhibit the growth of harmful microorganisms and its high protease activity. In this study, Bacillus subtilis was used to ferment gluten and assess the effects of the fermentation process on the physicochemical, microstructure and antioxidant properties of gluten. The results of Fourier infrared spectroscopy (FT-IR) and circular chromatography (CD) showed a significant decrease in the content of α-helix structures and a significant increase in the content of ß-sheet structures in gluten after fermentation (p < 0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that glutenin was degraded into small molecular peptides with a molecular weight of less than 26 kDa after 24 h of fermentation; meanwhile, the fermentation process significantly increased the free amino acid content of the samples (p < 0.05), reaching 1923.38 µg/mL at 120 h of fermentation, which was 39.46 times higher than that at 24 h of fermentation (p < 0.05). In addition, the fermented back gluten has higher free radical scavenging activity and iron reduction capacity. Therefore, fermented gluten may be used as a functional food to alleviate oxidative stress. This study provides a reference for the high-value application of gluten.

The Potential Use of Fungal Co-Culture Strategy for Discovery of New Secondary Metabolites.

Fungi are an important and prolific source of secondary metabolites (SMs) with diverse chemical structures and a wide array of biological properties. In the past two decades, however, the number of new fungal SMs by traditional monoculture method had been greatly decreasing. Fortunately, a growing number of studies have shown that co-culture strategy is an effective approach to awakening silent SM biosynthetic gene clusters (BGCs) in fungal strains to produce cryptic SMs. To enrich our knowledge of this approach and better exploit fungal biosynthetic potential for new drug discovery, this review comprehensively summarizes all fungal co-culture methods and their derived new SMs as well as bioactivities on the basis of an extensive literature search and data analysis. Future perspective on fungal co-culture study, as well as its interaction mechanism, is supplied.

Auricular Acupressure for Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: The purpose of this systematic review was to summarize the current evidence to examine the safety and effectiveness of auricular acupressure on dry eye diseases. Materials and Methods: Twenty databases were searched from their inception until November 2022. Only randomized controlled trials (RCTs) in which auricular acupressure was used for dry eye diseases were included. The selection process, data extraction and quantitative were conducted according to the guidelines. Results: Seven RCTs met the inclusion criteria. Meta-analysis showed that compared to artificial tears, auricular acupressure had a favorable effect on prolonging tear breakup time (TBUT), improving the Schirmer I test (SIT) score and the score of symptoms (SOS) of patients with dry eye disease (p < 0.05). Furthermore, compared to the artificial tears alone, auricular acupressure plus artificial tears had a significantly greater SIT score (p < 0.001) and response rate (p = 0.006), significantly longer TBUT (p < 0.001), and significantly lower Ocular surface disease index (OSDI) (p = 0.02) and SOS (p = 0.03). However, there was no statistically significant difference between the auricular acupressure plus artificial tears group and the artificial tears group in terms of cornea fluorescein staining (CFS) (p = 0.09). Conclusions: Auricular acupressure, as a sole intervention or in combination with artificial tears, may have a beneficial effect on dry eye disease. However, more high-quality RCTs need to be included in the future to further prove the positive effects of auricular acupressure on patients with dry eye disease.

Effects of Ground Slopes on Erector Spinae Muscle Activities and Characteristics of Golf Swing.

(1) Background: 'Slope' refers to the position faced by golfers on the course. Research on the recruitment strategies of thoracolumbar erector spinae during golf swings on different slopes may help us to understand some underlying mechanisms of lower back pain. (2) Purpose: The purpose of the present study is to assess electromyography (EMG) patterns of the erector spinae muscles (ES) and the kinematics of the trunk and swing parameters while performing golf swings on three different ground slopes: (1) no slope where the ball is level with the feet (BLF), (2) a slope where the ball is above the feet (BAF), and (3) a slope where the ball is below the feet (BBF). Furthermore, the present study evaluates the effect of slope on the kinematics of the trunk, the X-factor angle, and the hitting parameters. (3) Methods: Eight right-handed recreational male golfers completed five swings using a seven-iron for each ground slope. Surface electromyograms from the left and right sides of the ES thoracolumbar region (T8 and L3 on the spinous process side) were evaluated. Each golf swing was divided into five phases. Kinematics of the shoulder, trunk, and spine were evaluated, and the ball speed, swing speed, carry, smash factor, launch angle, and apex were measured using Caddie SC300. (3) Results: The muscle activity of the BAF and BBF slopes was significantly lower than that of the BLF slope during the early follow-through phase of the thoracic ES on the lead side (i.e., left side) and during the acceleration and early follow-through phases of the lumbar ES on the lead side. The lead and trail side (i.e., right side) lumbar ES were more active during acceleration than the thoracic ES. Additionally, the trends of the lead and trail sides of the thoracolumbar regions on the three slopes were found to be the same across the five phases. Trunk angle and X-factor angles had no significant differences in address, top of backswing, or ball impact. The maximum separation angles of the X-factor appeared in the early phase of the downswing for all the three slopes. Regarding smash factor and launch angle, there were no significant differences between the three slopes. The ball speed, swing speed, carry, and apex were higher on BLF than on BAF and BBF slopes. (4) Conclusion: The findings suggest that amateur golfers face different slopes with altered muscle recruitment strategies. Specifically, during the acceleration phase of the golf swing, the BAF and the BBF slopes, compared with the BLF slope, significantly underactivated the lead side thoracolumbar erector spinae muscles, thereby increasing the risk of back injury. Changes in muscle activity during critical periods may affect neuromuscular deficits in high-handicap players and may have implications for the understanding and development of golf-related lower back pain. In addition, the X-factor angle was not affected by the slope, however, it can be found that the hitting parameters on the BLF slope are more dominant than on the other slopes.

Highly efficient and robust π-FISH rainbow for multiplexed in situ detection of diverse biomolecules.

In the unprecedented single-cell sequencing and spatial multiomics era of biology, fluorescence in situ hybridization (FISH) technologies with higher sensitivity and robustness, especially for detecting short RNAs and other biomolecules, are greatly desired. Here, we develop the robust multiplex π-FISH rainbow method to detect diverse biomolecules (DNA, RNA, proteins, and neurotransmitters) individually or simultaneously with high efficiency. This versatile method is successfully applied to detect gene expression in different species, from microorganisms to plants and animals. Furthermore, we delineate the landscape of diverse neuron subclusters by decoding the spatial distribution of 21 marker genes via only two rounds of hybridization. Significantly, we combine π-FISH rainbow with hybridization chain reaction to develop π-FISH+ technology for short nucleic acid fragments, such as microRNA and prostate cancer anti-androgen therapy-resistant marker ARV7 splicing variant in circulating tumour cells from patients. Our study provides a robust biomolecule in situ detection technology for spatial multiomics investigation and clinical diagnosis.

Auricular Acupressure for Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: The purpose of this systematic review was to summarize the current evidence to examine the safety and effectiveness of auricular acupressure on dry eye diseases. Materials and Methods: Twenty databases were searched from their inception until November 2022. Only randomized controlled trials (RCTs) in which auricular acupressure was used for dry eye diseases were included. The selection process, data extraction and quantitative were conducted according to the guidelines. Results: Seven RCTs met the inclusion criteria. Meta-analysis showed that compared to artificial tears, auricular acupressure had a favorable effect on prolonging tear breakup time (TBUT), improving the Schirmer I test (SIT) score and the score of symptoms (SOS) of patients with dry eye disease (p < 0.05). Furthermore, compared to the artificial tears alone, auricular acupressure plus artificial tears had a significantly greater SIT score (p < 0.001) and response rate (p = 0.006), significantly longer TBUT (p < 0.001), and significantly lower Ocular surface disease index (OSDI) (p = 0.02) and SOS (p = 0.03). However, there was no statistically significant difference between the auricular acupressure plus artificial tears group and the artificial tears group in terms of cornea fluorescein staining (CFS) (p = 0.09). Conclusions: Auricular acupressure, as a sole intervention or in combination with artificial tears, may have a beneficial effect on dry eye disease. However, more high-quality RCTs need to be included in the future to further prove the positive effects of auricular acupressure on patients with dry eye disease.

The FabA-FabB Pathway Is Not Essential for Unsaturated Fatty Acid Synthesis but Modulates Diffusible Signal Factor Synthesis in Xanthomonas campestris pv. campestris.

Most bacteria use type II fatty acid synthesis (FAS) systems for synthesizing fatty acids, of which the conserved FabA-FabB pathway is considered to be crucial for unsaturated fatty acid (UFA) synthesis in gram-negative bacteria. Xanthomonas campestris pv. campestris, the phytopathogen of black rot disease in crucifers, produces higher quantities of UFAs under low-temperature conditions for increasing membrane fluidity. The fabA and fabB genes were identified in the X. campestris pv. campestris genome by BLAST analysis; however, the growth of the X. campestris pv. campestris fabA and fabB deletion mutants was comparable to that of the wild-type strain in nutrient and minimal media. The X. campestris pv. campestris ΔfabA and ΔfabB strains produced large quantities of UFAs and, altogether, these results indicated that the FabA-FabB pathway is not essential for growth or UFA synthesis in X. campestris pv. campestris. We also observed that the expression of X. campestris pv. campestris fabA and fabB restored the growth of the temperature-sensitive Escherichia coli fabA and fabB mutants CL104 and CY242, respectively, under non-permissive conditions. The in-vitro assays demonstrated that the FabA and FabB proteins of X. campestris pv. campestris catalyzed FAS. Our study also demonstrated that the production of diffusible signal factor family signals that mediate quorum sensing was higher in the X. campestris pv. campestris ΔfabA and ΔfabB strains and greatly reduced in the complementary strains, which exhibited reduced swimming motility and attenuated host-plant pathogenicity. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

KIF3A inhibits nasopharyngeal carcinoma proliferation, migration and invasion by interacting with ß-catenin to suppress its nuclear accumulation.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor prevalent in southern China and Southeast Asia. Previous studies have shown that Kinesin Family Member 3A (KIF3A) plays a critical role in the oncogenesis of various cancer types. However, the role of KIF3A in NPC tumorigenesis and the mechanism underlying its function have not been reported. In this study, we found that KIF3A was significantly downregulated in NPC cells and tissues, and KIF3A expression in NPC patients was associated with tumor stage and was positively corrected with overall survival. In vitro and in vivo experiments indicated that overexpression of KIF3A inhibited NPC cell proliferation, migration, and invasion. Mechanistic studies found that KIF3A bound ß-catenin and attenuated ß-catenin aggregation in the nucleus. Moreover, rescue experiments demonstrated that the inhibitory effect of KIF3A on NPC proliferation, migration and invasion was partially dependent on ß-catenin. Taken together, our data suggest that KIF3A interacts with ß-catenin and attenuates NPC proliferation, migration, and invasion by suppressing the intranuclear aggregation of ß-catenin. KIF3A may be a promising therapeutic target of patients with NPC.

Circulating tumor DNA profile and its clinical significance in patients with hormone receptor-positive and HER2-negative mBC.

Background: After early-line (first- and second-line) endocrine therapy, hormone-receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancers (mBCs) become resistant to endocrine therapy. Genetic alterations may underlie resistance to endocrine therapies. This study aims to investigate the circulating tumor DNA (ctDNA) alterations and the clinical implication in hormone-receptor-positive, HER2-negative metastatic breast cancer patients with multiline endocrine therapy failure. Methods: This registered study (NCT05079074, ClinicalTrials.gov) enrolled 104 patients with hormone-receptor-positive, HER2-negative metastatic breast cancer who progressed after the early-line endocrine therapy. ctDNA alterations were analyzed by next generation sequencing (NGS). ctDNA alterations were ranked and clustered by using R 'ComplexHeatmap' and 'hclust' function. ctDNA-guided therapy was administrated. Progression-free survival (PFS) was assessed COX regression analysis, and Kaplan-Meier curves were plotted. Findings: The top ctDNA altered genes were TP53 (39%), PIK3CA (38%), BRCA1/2 (13%), ESR1 (12%), FGFR (11%), ERBB2 (11%), and GATA3 (9%). Among these genes, TP53, PIK3CA helix domain mutation (PIK3CA-HD), FGFR, ESR1 and GATA3 were related to endocrine therapy resistance. The genetic landscapes changed and tumor mutation burden increased in both TP53-altered and PIK3CA-altered patients. Both BRCA1/2 and ERBB2 alterations correlated with TP53 alterations (P=0.02 and P=0.04, respectively). However, while 93% BRCA1/2 alterations concentrated in PIK3CA-wildtype patients, 82% ERBB2 alterations concentrated in PIK3CA-altered patients. Kaplan-Meier curves showed that patients who received druggable ctDNA alteration-guided treatment (DDAT) had significantly longer PFS than those who received physician-chosen therapy, with median PFS of 6.1 months versus 4.6 months (hazard ratio = 0.53, 95% CI: 0.34-0.85, Logrank P = 0.006). Conclusion: Multiple genetic alterations were important reasons for the failure of endocrine therapy for HR-positive and HER2-negative mBC. Targeting these genes might restore the treatment sensitivity and benefit survival.

Correlation of Lower Limb Muscle Activity with Knee Joint Kinematics and Kinetics during Badminton Landing Tasks.

A study on a single-leg landing task after an overhead stroke in badminton suggests that poor knee biomechanical indicators may be a risk factor for anterior cruciate ligament (ACL) injury. A preventive program targeting neuromuscular control strategies is said to alter the biomechanics of the knee joint and have a beneficial effect on reducing ACL injury. However, the relationship between muscle activity around the knee joint and knee biomechanical risk factors in the badminton landing task is unclear. The purpose of this study was to investigate the relationship between this movement pattern of muscle activity and knee kinematics and kinetics. This experiment analyzed knee muscle activity and biomechanical information in a sample of 34 badminton players (17 male, 17 female) during a badminton landing task. We assessed the relationship between the rectus femoris (RF), medial hamstring (MHAM), lateral hamstring (LHAM), medial gastrocnemius (MGAS), lateral gastrocnemius (LGAS), medial and lateral hamstring to quadriceps co-contraction ratio (MH/Q and LH/Q) with the knee flexion angle, valgus angle, extension moment, valgus moment, and proximal tibial anterior shear force. A moderate negative correlation was found between the peak knee flexion angle and electromyography (EMG) activity in LGAS (r = 0.47, p = 0.0046, R2 = 0.23, 95% CI: 0.16 to 0.70). Peak proximal tibial shear force showed strong and positive correlations with RF EMG activity (r = 0.52, p = 0.0016, R2 = 0.27, 95% CI: 0.22 to 0.73) and strong and negative correlations with MH/Q (r = 0.50, p = 0.0023, R2 = 0.25, 95% CI: 0.20 to 0.72). The knee extension moment showed moderate and positive correlations with RF EMG activity (r = 0.48, p = 0.0042, R2 = 0.23, 95% CI: 0.17 to 0.70) and strong and negative correlations with MH/Q (r = 0.57, p = 0.0004, R2 = 0.33, 95% CI: 0.29 to 0.76). The peak knee valgus moment showed strong and positive correlations with LH/Q (r = 0.55, p = 0.0007, R2 = 0.31, 95% CI: 0.26 to 0.75). Our findings suggest that there is a correlation between lower extremity muscle activity and knee kinematics and kinetics during the single-leg landing task in badminton; therefore, lower extremity muscle activity should be considered when developing rehabilitation or injury prevention programs.

Artificial intelligence scale-invariant feature transform algorithm-based system to improve the calculation accuracy of Ki-67 index in invasive breast cancer: a multicenter retrospective study.

Background: Ki-67 is a key indicator of the proliferation activity of tumors. However, no standardized criterion has been established for Ki-67 index calculation. Scale-invariant feature transform (SIFT) algorithm can identify the robust invariant features to rotation, translation, scaling and linear intensity changes for matching and registration in computer vision. Thus, this study aimed to develop a SIFT-based computer-aided system for Ki-67 calculation in breast cancer. Methods: Hematoxylin and eosin (HE)-stained and Ki-67-stained slides were scanned and whole slide images (WSIs) were obtained. The regions of breast cancer (BC) tissues and non-BC tissues were labeled by experienced pathologists. All the labeled WSIs were randomly divided into the training set, verification set, and test set according to a fixed ratio of 7:2:1. The algorithm for identification of cancerous regions was developed by a ResNet network. The registration process between paired consecutive HE-stained WSIs and Ki-67-stained WSIs was based on a pyramid model using the feature matching method of SIFT. After registration, we counted the nuclear-stained Ki-67-positive cells in each identified invasive cancerous region using color deconvolution. To assess the accuracy, the AI-assisted result for each slice was compared with the manual diagnosis result of pathologists. If the difference of the two positive rate values is not greater than 10%, it was a consistent result; otherwise, it was an inconsistent result. Results: The accuracy of the AI-based algorithm in identifying breast cancer tissues in HE-stained slides was 93%, with an area under the curve (AUC) of 0.98. After registration, we succeeded in identifying Ki-67-positive cells among cancerous cells across the entire WSIs and calculated the Ki-67 index, with an accuracy rate of 91.5%, compared to the gold standard pathological reports. Using this system, it took about 1 hour to complete the evaluation of all the tested 771 pairs of HE- and Ki-67-stained slides. Each Ki-67 result took less than 2 seconds. Conclusions: Using a pyramid model and the SIFT feature matching method, we developed an AI-based automatic cancer identification and Ki-67 index calculation system, which could improve the accuracy of Ki-67 index calculation and make the data repeatable among different hospitals and centers.

Bismuth nanoparticles embedded in a carbon skeleton as an anode for high power density potassium-ion batteries.

Bismuth is a promising anode for potassium-ion batteries (PIBs) due to its suitable redox potential, large theoretical capacity, and superior electronic conductivity. Herein, we report a Bi@C (Bi nanoparticles uniformly embedded in a carbon skeleton) composite anode which delivers a superior rate performance of 244.3 mA h g-1 at 10.0 A g-1 and a reversible capacity of 255.6 mA h g-1 after 200 cycles in an optimized ether-based electrolyte. The outstanding electrochemical performance results from its robust structural design with fast reaction kinetics, which are confirmed by both experimental characterization studies and first-principles calculations. The reversible potassium storage mechanism of the Bi@C composite was also investigated by in situ X-ray diffraction. In addition, the full PIB cell assembled with a Bi@C composite anode and nickel-based Prussian blue analogue cathode exhibits high discharge voltage (3.18 V), remarkable power density (>10 kW kg-1), and an excellent capacity retention of 87.8% after 100 cycles. The results demonstrate that the PIBs with Bi anodes are promising candidates for power-type energy storage devices.

Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses.

Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5-1.75-Å resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection.

Cobalt-Catalyzed Effective Access to Quinoxalines with Insights in Annulation of Terminal Alkynes and o-Phenylenediamines.

A novel methodology for the annulation of terminal alkynes and o-phenylenediamines by using a combination of a cobalt catalyst and oxygen as a terminal oxidant is reported. This method shows wide substrate scope and good functional group tolerance and provides a wide range of quinoxalines in good to high yields. The method is demonstrated by its gram-scale and broad potential applications. Furthermore, this protocol serves as a powerful tool for the late-stage functionalization of various complex bioactive molecules and drugs to provide a new class of molecules containing two distinct bioactive molecules directly linked. Detailed mechanistic studies reveal that the current reaction goes through a novel mechanism different from the previously reported glyoxal mechanism.

Functional metabolomics revealed the dual-activation of cAMP-AMP axis is a novel therapeutic target of pancreatic cancer.

Pancreatic cancer (PC) is one of the most malignant cancers, owing to extremely high aggressiveness and mortality. Yet, this condition currently incurs widely drug resistance and therapeutic deficiency. In this study, we proposed a novel functional metabolomics strategy as Spatial Temporal Operative Real Metabolomics (STORM) to identify the determinant functional metabolites in a dynamic and visualized pattern whose level changes are mechanistically associated with therapeutic efficiency of gemcitabine against PC. Integrating quantitative analysis and spatial-visualization characterization of functional metabolites in vivo, we identified that the AMP-cAMP axis was a novel therapeutic target of PC to intermediate therapeutic efficiency of gemcitabine. Gemcitabine could induce the dual accumulation of cyclic AMP (cAMP) and AMP in tumor tissues. Quantitative analysis of associated biosynthetic enzymes and genes revealed that two independent intracellular ATP derived biosynthetic pathways to promote the dual activation of AMP-cAMP axis in a lower-level energetic environment. Then, gemcitabine induced the dual accumulation of AMP and cAMP can separately activate signaling pathways of AMPK and PKA, leading to the inhibition of tumor growth by the upregulation of the downstream tumor suppressor GADD45A. Collectively, our new STORM strategy was the first time to identify novel target of PC from a metabolic perspective as the dual activation of AMP-cAMP axis induced by gemcitabine can efficiently suppress PC tumor growth. In addition, such discovery has the capability to lower drug resistance of gemcitabine by specifically interacting with novel target, contributing to the improvement of therapeutic efficiency.

Growth characteristics of Cunninghamia lanceolata in China.

Chinese fir (Cunninghamia lanceolata) is one of southern China's most important native tree species, which has experienced noticeable climate-induced changes. Published papers (1978-2020) on tree growth of Chinese fir forests in China were collected and critically reviewed. After that, a comprehensive growth data set was developed from 482 sites, which are distributed between 102.19° and 130.07°E in longitude, between 21.87° and 37.24°N in latitude and between 5 and 2260 m in altitude. The dataset consists of 2265 entries, including mean DBH (cm), mean H (m), volume (m3), biomass (dry weight) (kg) (stem (over bark) biomass, branches biomass, leaves biomass, bark biomass, aboveground biomass, roots biomass, total trees biomass) and related information, i.e. geographical location (Country, province, study site, longitude, latitude, altitude, slope, and aspect), climate (mean annual precipitation-MAP and mean annual temperature-MAT), stand description (origin, age, canopy density and stand density), and sample regime (plot size, number and investigation year). Our results showed that (1) the best prediction of height was obtained using nonlinear composite model Height = [Formula: see text], (R2 = 0.8715, p < 0.05), (2) the equation Volume = DBH2/(387.8 + 19,190/Height) (R2 = 0.9833, p < 0.05) was observed to be the most suitable model for volume estimation. Meanwhile, when the measurements of the variables are difficult to carry out, the volume model Volume = 0.03957 - 0.01215*DBH + 0.00118*DBH2 (R2 = 0.9573, p < 0.05) is determined from DBH only has a practical advantage, (3) the regression equations of component biomass against DBH explained more significant than 86% variability in almost all biomass data of woody tissues, which were ranked as total trees (97.25%) > aboveground (96.55%) > stems (with bark) (96.17%) > barks (88.95%) > roots (86.71%), and explained greater than 64% variability in branch biomass. The foliage biomass equation was the poorest among biomass components (R2 = 0.6122). The estimation equations derived in this study are particularly suitable for the Chinese fir forests in China. This dataset can provide a theoretical basis for predicting and assessing the potential of carbon sequestration and afforestation activities of Chinese fir forests on a national scale.

Decoding the spatial chromatin organization and dynamic epigenetic landscapes of macrophage cells during differentiation and immune activation.

Immunocytes dynamically reprogram their gene expression profiles during differentiation and immunoresponse. However, the underlying mechanism remains elusive. Here, we develop a single-cell Hi-C method and systematically delineate the 3D genome and dynamic epigenetic atlas of macrophages during these processes. We propose "degree of disorder" to measure genome organizational patterns inside topologically-associated domains, which is correlated with the chromatin epigenetic states, gene expression, and chromatin structure variability in individual cells. Furthermore, we identify that NF-κB initiates systematic chromatin conformation reorganization upon Mycobacterium tuberculosis infection. The integrated Hi-C, eQTL, and GWAS analysis depicts the atlas of the long-range target genes of mycobacterial disease susceptible loci. Among these, the SNP rs1873613 is located in the anchor of a dynamic chromatin loop with LRRK2, whose inhibitor AdoCbl could be an anti-tuberculosis drug candidate. Our study provides comprehensive resources for the 3D genome structure of immunocytes and sheds insights into the order of genome organization and the coordinated gene transcription during immunoresponse.