Determinants of macaques' space use: A test for the ecological constraints model using GPS collars.

As a central topic in Behavioral Ecology, animal space use involves dynamic responses to social and ecological factors. We collared 22 rhesus macaques (Macaca mulatta) from six groups on Neilingding Island, China, and collected 80,625 hourly fixes over a year. Using this high-resolution location data set, we quantified the macaques' space use at the individual level and tested the ecological constraints model while considering various environmental and human interfering factors. As predicted by the ecological constraints model, macaques in larger groups had longer daily path lengths (DPLs) and larger home ranges. We found an inverted U-shape relationship between mean daily temperatures and DPLs, indicating that macaques traveled farther on mild temperature days, while they decreased DPLs when temperatures were too high or too low. Anthropogenic food subsidies were positively correlated to DPLs, while the effect of rainfall was negative. Macaques decreased their DPLs and core areas when more flowers and less leaves were available, suggesting that macaques shifted their space use patterns to adapt to the seasonal differences in food resources. By applying GPS collars on a large number of individuals living on a small island, we gained valuable insights into within-group exploitation competition in wild rhesus macaques.

Protocol for the Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study: a prospective, observational, multicentre cohort study of acute spinal cord injury.

INTRODUCTION: Spinal cord injury (SCI) is a catastrophic event with devastating physical, social and occupational consequences for patients and their families. The number of patients with acute SCI in China continues to grow rapidly, but there have been no large prospective cohort studies of patients with acute SCI. This proposed study aims to establish a multicentre, extensive sample cohort of clinical data and biological samples of patients in China, which would aid the systematisation and standardisation of clinical research and treatment of acute SCI, thus reducing the heavy burden of acute SCI on patients and society. METHODS AND ANALYSIS: The Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study is an observational, multicentre cohort study of patients with acute SCI admitted to the Qilu Hospital of Shandong University and other participating centres with prospective collection of their clinical data and biological samples. We aim to recruit 2097 patients in this study. Demographics, disease history, emergency intervention information, motor and sensory examinations, surgical information, medication information and rehabilitation evaluation will be recorded. This will facilitate the development of a prediction model for complications and prognosis of patients with acute SCI and an evaluation of the current management of acute SCI. Among these variables, detailed information on surgical treatment will also be used to assess procedures for acute SCI treatment. Outcome measurements, including the International Standard for Neurological Classification of Spinal Cord Injury examinations, the occurrence of complications and death, will be performed repeatedly during follow-up. We will analyse imaging data and blood samples to develop SCI imaging markers and biomarkers. ETHICS AND DISSEMINATION: This study protocol has been approved by the Medical Ethics Committee of the Qilu Hospital of Shandong University and all other participating centres. The findings will be disseminated in peer-reviewed journals and academic conferences.

Design, Synthesis, and Mode of Action of Thioacetamide Derivatives as the Algicide Candidate Based on Active Substructure Splicing Strategy.

Lakes and reservoirs worldwide are experiencing a growing problem with harmful cyanobacterial blooms (HCBs), which have significant implications for ecosystem health and water quality. Algaecide is an effective way to control HCBs effectively. In this study, we applied an active substructure splicing strategy for rapid discovery of algicides. Through this strategy, we first optimized the structure of the lead compound S5, designed and synthesized three series of thioacetamide derivatives (series A, B, C), and then evaluated their algicidal activities. Finally, compound A3 with excellent performance was found, which accelerated the process of discovering and developing new algicides. The biological activity assay data showed that A3 had a significant inhibitory effect on M. aeruginosa. FACHB905 (EC50 = 0.46 µM) and Synechocystis sp. PCC6803 (EC50 = 0.95 µM), which was better than the commercial algicide prometryn (M. aeruginosa. FACHB905, EC50 = 6.52 µM; Synechocystis sp. PCC6803, EC50 = 4.64 µM) as well as better than lead compound S5 (M. aeruginosa. FACHB905, EC50 = 8.80 µM; Synechocystis sp. PCC6803, EC50 = 7.70 µM). The relationship between the surface electrostatic potential, chemical reactivity, and global electrophilicity of the compounds and their activities was discussed by density functional theory (DFT). Physiological and biochemical studies have shown that A3 might affect the photosynthesis pathway and antioxidant system in cyanobacteria, resulting in the morphological changes of cyanobacterial cells. Our work demonstrated that A3 might be a promising candidate for the development of novel algicides and provided a new active skeleton for the development of subsequent chemical algicides.

Engineered poly(A)-surrogates for translational regulation and therapeutic biocomputation in mammalian cells.

Here, we present a gene regulation strategy enabling programmable control over eukaryotic translational initiation. By excising the natural poly-adenylation (poly-A) signal of target genes and replacing it with a synthetic control region harboring RNA-binding protein (RBP)-specific aptamers, cap-dependent translation is rendered exclusively dependent on synthetic translation initiation factors (STIFs) containing different RBPs engineered to conditionally associate with different eIF4F-binding proteins (eIFBPs). This modular design framework facilitates the engineering of various gene switches and intracellular sensors responding to many user-defined trigger signals of interest, demonstrating tightly controlled, rapid and reversible regulation of transgene expression in mammalian cells as well as compatibility with various clinically applicable delivery routes of in vivo gene therapy. Therapeutic efficacy was demonstrated in two animal models. To exemplify disease treatments that require on-demand drug secretion, we show that a custom-designed gene switch triggered by the FDA-approved drug grazoprevir can effectively control insulin expression and restore glucose homeostasis in diabetic mice. For diseases that require instantaneous sense-and-response treatment programs, we create highly specific sensors for various subcellularly (mis)localized protein markers (such as cancer-related fusion proteins) and show that translation-based protein sensors can be used either alone or in combination with other cell-state classification strategies to create therapeutic biocomputers driving self-sufficient elimination of tumor cells in mice. This design strategy demonstrates unprecedented flexibility for translational regulation and could form the basis for a novel class of programmable gene therapies in vivo.

Generation and characterization of PBMCs-derived human induced pluripotent stem cell (iPSC) line SDQLCHi050-A from a healthy donor.

The human induced pluripotent stem cell (iPSC) line SDQLCHi050-A was derived from the PBMCs of a healthy 5-year-old male child. The karyotyping, pluripotency, and trilineage differentiation characteristics were verified in the SDQLCHi050-A line.

The metabolite profiling of YR-1702 injection in human plasma, urine and feces by HPLC-Q-TOF-MS/MS.

YR-1702, a hybrid µ/κ/δ receptor agonist, is modified from the traditional opioid analgesic dezocine. It had shown both excellent analgesic effect and lower addiction in phase I clinical trial in China, however, the metabolic pathway of YR-1702 in humans remains unelucidated.The goals of this study are to characterise the metabolism of YR-1702 in human liver microsomes (HLMs) and patients with chronic non-cancer pain by high performance liquid chromatography-coupled with quadrupole-time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS).The results showed that a total of twelve metabolites were identified in HLMs, in which 7, 6 and 5 metabolites were also found in human plasma, urine and feces, respectively. And the major metabolic pathways include mono-hydroxylation, di-hydroxylation, dehydrogenation and glucuronidation. The locations of hydroxylation and dehydrogenation were identified by the signature fragments of the metabolites.The relative contents of the metabolites in human plasma were also evaluated, in which the main metabolite M1 notably accounting for more than 14% of the total drug exposure. This study would contribute to the understanding of the in vivo metabolite profile of YR-1702 injection for future use.

A critical appraisal of clinical practice guidelines on surgical treatments for spinal cord injury.

BACKGROUND CONTEXT: Spinal cord injury (SCI) is a global health problem with a heavy economic burden. Surgery is considered as the cornerstone of SCI treatment. Although various organizations have formulated different guidelines on surgical treatment for SCI, the methodological quality of these guidelines has still not been critically appraised. PURPOSE: We aim to systematically review and appraise the current guidelines on surgical treatments of SCI and summarize the related recommendations with the quality evaluation of supporting evidence. STUDY DESIGN: Systematic review. METHODS: Medline, Cochrane library, Web of Science, Embase, Google Scholar, and online guideline databases were searched from January 2000 to January 2022. The most updated and recent guidelines containing evidence-based or consensus-based recommendations and established by authoritative associations were included. The Appraisal of Guidelines for Research and Evaluation, 2nd edition instrument containing 6 domains (eg, applicability) was used to appraise the included guidelines. An evidence-grading scale (ie, level of evidence, LOE) was utilized to evaluate the quality of supporting evidence. The supporting evidence was categorized as A (the best quality), B, C, and D (the worst quality). RESULTS: Ten guidelines from 2008 to 2020 were included, however, all of them acquired the lowest scores in the domain of applicability among all the six domains. Fourteen recommendations (eight evidence-based recommendations and six consensus-based recommendations) were totally involved. The SCI types of the population and timing of surgery were studied. Regarding the SCI types of the population, eight guidelines (8/10, 80%), two guidelines (2/10, 20%), and three guidelines (3/10, 30%) recommended surgical treatment for patients with SCI without further clarification of characteristics, incomplete SCI, and traumatic central cord syndrome (TCCS), respectively. Besides, one guideline (1/10, 10%) recommended against surgery for patients with SCI without radiographic abnormality. Regarding the timing of surgery, there were eight guidelines (8/10, 80%), two guidelines (2/10, 20%), and two guidelines (2/10, 20%) with recommendations for patients with SCI without further clarification of characteristics, incomplete SCI, and TCCS, respectively. For patients with SCI without further clarification of characteristics, all eight guidelines (8/8, 100%) recommended for early surgery and five guidelines (5/8, 62.5%) recommended for the specific timing, which ranged from within 8 hours to within 48 hours. For patients with incomplete SCI, two guidelines (2/2, 100%) recommended for early surgery, without specific time thresholds. For patients with TCCS, one guideline (1/2, 50%) recommended for surgery within 24 hours, and another guideline (1/2, 50%) simply recommended for early surgery. The LOE was B in eight recommendations, C in three recommendations, and D in three recommendations. CONCLUSIONS: We remind the reader that even the highest quality guidelines often have significant flaws (eg, poor applicability), and some of the conclusions are based on consensus recommendations which is certainly less than ideal. With these caveats, we found most included guidelines (8/10, 80%) recommended early surgical treatment for patients after SCI, which was consistent between evidence-based recommendations and consensus-based recommendations. Regarding the specific timing of surgery, the recommended time threshold did vary, but it was usually within 8 to 48 hours, where the LOE was B to D.

Generation and characterization of PBMCs-derived human induced pluripotent stem cell (iPSC) line SDQLCHi051-A from an autism spectrum disorder patient with compound CHD8 gene mutations.

CHD8 mutation is a case of genetic related autism spectrum disorder(ASD), In our research, We describe here the derivation of the iPSC line SDQLCHi051-A from a patient with autism spectrum disorder (ASD) due to two heterozygote mutations (c.6728G > A and c.3876 T > G) in the CHD8 gene. The resulting iPSC line has typical iPSCs characteristics, including pluripotency and trilineage differentiation hallmarks.

[Regulatory effects of umbilical cord mesenchymal stem cells and their conditioned medium on gut microbiota of septic mice].

OBJECTIVE: To investigate and compare the regulatory effects of umbilical cord mesenchymal stem cells (MSC) and their conditioned medium (MSC-CM) on gut microbiota of septic mice. METHODS: Twenty-eight six-to-eight-week-old female C57BL/6J mice were randomly divided into sham operation group (Sham group), sepsis model group (CLP group), sepsis+MSC treatment group (CLP+MSC group) and sepsis+MSC-CM treatment group (CLP+MSC-CM group), with seven mice in each group. The septic mouse model was established by cecal ligation and puncture (CLP). In Sham group, CLP were not performed, and other operations were the same as CLP group. Mice in the CLP+MSC group and CLP+MSC-CM group received 0.2 mL 1×106 MSC or 0.2 mL concentrated MSC-CM via intraperitoneal injection 6 hours after CLP, respectively. Sham group and CLP group were given 0.2 mL sterile phosphate buffer saline (PBS) via intraperitoneal injection. Histopathological changes were evaluated by hematoxylin-eosin (HE) staining and colon length. Levels of inflammatory factors in serum were detected by enzyme-linked immunosorbent assay (ELISA). Phenotype of peritoneal macrophages was analyzed by flow cytometry, and the gut microbiota was analyzed via 16S rRNA sequencing. RESULTS: Compared with Sham group, significant inflammatory injury in lung and colon was observed, and shorter colon was detected in CLP group (cm: 6.00±0.26 vs. 7.11±0.09), the level of inflammatory cytokine interleukin-1ß (IL-1ß) in serum was significantly increased (ng/L: 432.70±17.68 vs. 353.70±17.01), the proportion of F4/80+ peritoneal macrophages was increased [(68.25±3.41)% vs. (50.84±4.98)%], while the ratio of F4/80+CD206+ anti-inflammatory peritoneal macrophages was decreased [(45.25±6.75)% vs. (66.66±3.36)%]. The α diversity sobs index of gut microbiota was downregulated significantly (118.50±23.25 vs. 255.70±6.87), the structure of species composition was altered, and the relative abundance of functional gut microbiota related to transcription, secondary metabolites biosynthesis, transport and catabolism, carbohydrate transport and metabolism, and signal transduction were decreased significantly in CLP group (all P < 0.05). Compared with CLP group, upon MSC or MSC-CM treatment, the pathological injury in lung and colon was alleviated to varying extent, the length of colon was increased (cm: 6.53±0.27, 6.87±0.18 vs. 6.00±0.26), the level of IL-1ß in serum was downregulated (ng/L: 382.10±16.93, 343.20±23.61 vs. 432.70±17.68), the ratio of F4/80+ peritoneal macrophages was decreased [(47.65±3.93)%, (48.68±2.51)% vs. (68.25±3.41)%], the ratio of F4/80+CD206+ anti-inflammatory peritoneal macrophages was increased [(52.73±5.02)%, (66.38±4.73)% vs. (45.25±6.75)%], and the α diversity sobs index of gut microbiota was increased (182.50±16.35, 214.00±31.18 vs. 118.50±23.25), and the effects of MSC-CM were more significant (all P < 0.05). At the same time, species composition of gut microbiota was rebuilt, and a tendency of increase in relative abundance of functional gut microbiota was observed upon MSC and MSC-CM treatment. CONCLUSIONS: Both MSC and MSC-CM could alleviate inflammatory injury in tissues, and showed regulatory effects on gut microbiota in septic mouse model, moreover, MSC-CM exhibited superior advantages over MSC.

A critical appraisal of clinical practice guidelines for diagnostic imaging in the spinal cord injury.

BACKGROUND CONTEXT: Spinal cord injury (SCI) is a serious health problem which carries a heavy economic burden. Imaging technologies play an important role in the diagnosis of SCI. Although several organizations have developed guidelines for diagnostic imaging of SCI, their quality has not yet been systematically assessed. PURPOSE: We aim to conduct a systematic review to appraise SCI guidelines and summarize their recommendations for diagnostic imaging of SCI. STUDY DESIGN: Systematic review. METHODS: We searched Embase, Medline, Web of Science, Cochrane, some guideline-specific databases (eg, Scottish Intercollegiate Guidelines Network) and Google Scholar from January 2000 to January 2022. We included guidelines developed by nationally recognized organizations. If multiple versions could be obtained, we included the latest one. We appraised included guidelines using the Appraisal of Guidelines for Research and Evaluation, 2nd edition instrument which contains six domains (eg, scope and purpose). We also extracted recommendations and assessed their supporting evidence using levels of evidence (LOE). The evidence was categorized as A (the best quality), B, C, and D (the worst quality). RESULTS: Seven guidelines (2008-2020) were included. They all received the lowest scores in the domain of applicability. All guidelines (7/7, 100%) recommended magnetic resonance imaging (MRI) in patients with SCI or SCI without radiographic abnormality (SCIWORA). A total of 12 recommendations involving patient age (eg, adult and child patients), timing of MRI (eg, as soon as possible and in the acute period), symptoms indicated for MRI (eg, a stiff spine and midline tenderness, suspected disc and posterior ligamentous complex injury, and neurological deficit), and types of MRI (eg, T2-weighted imaging and diffusion tensor imaging) were extracted. Among them, the LOE was C in nine (75%) recommendations and D in three (25%) recommendations. CONCLUSIONS: Seven guidelines were included in the present systematic review, and all of them showed the worst applicability scores in the Appraisal of Guidelines for Research and Evaluation, 2nd edition instrument. They all weakly recommended MRI for patients with suspected SCI or SCIWORA based on a low LOE.

A critical appraisal of clinical practice guidelines for management of four common complications after spinal cord injury.

BACKGROUND CONTEXT: Complications such as pressure sores, pulmonary infection, urinary tract infection (UTI), and venous thromboembolism (VTE) are common after spinal cord injury (SCI). These have serious consequences for patients' physical, social, and vocational well-being. Several authoritative organizations have developed guidelines for managing these complications after SCI. PURPOSE: We aim to systematically review and appraise guidelines on the management of four common complications (pressure sores, pulmonary infection, UTI, and VTE) after SCI as well as to summarize relevant recommendations and assess the quality of their supporting evidence. DESIGN: Systematic review. METHODS: We searched Medline, Embase, Cochrane, and Web of Science, as well as guideline-specific databases (eg, National Guideline Clearinghouse) and Google Scholar, from January 2000 to January 2022. We included the most updated guidelines developed by specific authoritative organizations. We evaluated the included guidelines using the Appraisal of Guidelines for Research and Evaluation 2nd edition instrument, which measures six domains (eg, applicability). Recommendations extracted from guidelines were categorized as for, against, or neither for nor against. An evidence assessment was adopted to classify the quality of supporting evidence as poor, fair, or good. RESULTS: Eleven guidelines from 2005 to 2020 were included, all of which, among the six domains, scored lowest in the domain of applicability. For pressure sores, guidelines recommended for skin inspection, repositioning, and the use of pressure reduction equipment as preventive measures and dressings, debridement, and surgery as treatment measures. For pulmonary infection, guidelines recommended for physical (eg, the use of an insufflation-exsufflation device) and pharmacological measures (eg, the use of bronchodilators). For UTI, guidelines recommended for antibiotics as a treatment measure but recommended against cranberries, methenamine salts, and acidification or alkalinization agents as preventive measures. For VTE prophylaxis, five guidelines recommended for low molecular weight heparin (LMWH). Three guidelines recommended against unfractionated heparin, whereas one guideline recommended for it. Most of the supporting evidence was of poor quality (130/139), and the rest was of fair quality (9/139). CONCLUSIONS: For pressure sores, pulmonary infection, and UTI, evidence of poor to fair quality indicated consistent recommendations for prevention and treatment measures. For VTE, LMWH was consistently recommended, whereas recommendations on the use of unfractionated heparin were controversial.

A critical appraisal of clinical practice guidelines on pharmacological treatments for spinal cord injury.

BACKGROUND CONTEXT: Spinal cord injury brings devastating consequences and huge economic burden. Different authoritative organizations have developed different guidelines for pharmacological treatments of spinal cord injury, but there is a lack of a critical appraisal of them. PURPOSE: To systematically review and appraise guidelines regarding their recommendations for pharmacological treatments for spinal cord injury. STUDY DESIGN: Systematic review. METHODS: We searched Medline, Embase, Cochrane, and Web of Science from January 2000 to January 2022 as well as guideline-specific databases (eg, Congress of Neurological Surgeons) and Google Scholar. We included the most updated guideline containing evidence-based recommendations or consensus-based recommendations developed by specific authoritative organizations if multiple versions were available. We appraised guidelines through the Appraisal of Guidelines for Research and Evaluation, 2nd edition instrument consisting of six domains (eg, applicability). With supporting evidence, recommendations were classified as: for, against, neither for nor against. We utilized an evidence assessment system to categorize the quality of supporting evidence as poor, fair, or good. RESULTS: Eight guidelines developed from 2008 to 2020 were included, but all of them scored lowest in the domain of applicability among all six domains. Twelve pharmacological agents (eg, methylprednisolone) were studied. For methylprednisolone, three guidelines (3/8=37.5%) recommended for (one evidence-based and two consensus-based), three (3/8=37.5%) recommended against (all evidence-based), and two (2/8=25%) recommended neither for nor against. For monosialotetrahexosylganglioside (GM-1), one guideline (1/4=25%) recommended for (consensus-based), one (1/4=25%) recommended against (evidence-based), and two (2/4=50%) recommended neither for nor against. For other agents (eg, minocycline), most guidelines (3/5=60%) recommended neither for nor against, one (1/5=20%) recommended against naloxone (evidence-based) and nimodipine (evidence-based), and one (1/5=20%) recommended for neural growth factor (consensus-based). The quality of most of the supporting evidence was poor, and the rest was fair. CONCLUSIONS: There were inconsistencies among recommendations for methylprednisolone and GM-1. Evidence-based recommendations tended to recommend against, whereas consensus-based recommendations tended to recommend for.

Using One-Step Acid Leaching for the Recovering of Coal Gasification Fine Slag as Functional Adsorbents: Preparation and Performance.

Coal gasification fine slag (FS), a kind of by-product of coal chemical industry, was recovered for the preparation of functional adsorbents by acid leaching process, which was orthogonally optimized by HCl, HNO3, HF, HAc, and H2SO4. Methylene blue (MB) was used to evaluate the performance of functional adsorbents. The results demonstrated that 57.6% of the leaching efficiency (RLE) and 162.94 mg/g of adsorption capacity (CAC) of MB were achieved under the optimal conditions of HNO3 of 2.0 mol/L, acid leaching time of 2.0 h, and acid leaching temperature of 293K. The detections on X-ray Diffraction (XRD), Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and BET surface area (SBET) indicated that the synthesized functional adsorbents were characterized by mesoporous materials. The good fitting of adsorption process using pseudo-second-order and Langmuir models demonstrated that the chemisorption contributed to MB removal. The results of thermodynamics further revealed that the adsorption process of MB occurred spontaneously due to the exothermic properties. The work is expected to develop a novel and cost-effective strategy for the safe disposal of FS, and potentially offer an alternative pathway to increase the additional value for the coal chemical industry.

Sarcopenia: Body Composition and Gait Analysis.

Background: Age-induced sarcopenia negatively affects walking stability and increases the risk of falls, which is the leading cause of accidental death in the elderly. Objective: This study aimed to analyze and contrast body composition and gait characteristics in those with sarcopenia in relation to healthy controls to shed some light on the prevention of falls in elderly patients with sarcopenia. Materials and Methods: In this study, 68 community dwellers were scanned by the Hologic QDR-4500A Dual-energy X-ray absorptiometry (DXA). The appendicular lean mass index (ALMI) results were used to distinguish the normal participants from those with sarcopenia: 24 in the sarcopenia group, and 44 into the normal group. The participants were asked to undergo gait analysis on a plantar pressure measurement system. Statistical analysis was conducted to contrast both groups' gait and butterfly parameters from their gait test, and then a gait forward dynamics method was performed to quantify the analysis for both groups. Results: The ALMI of the female was not related to their age (r = 0.06) while that of the male was weakly related (r = 0.17). Body mass index (BMI) from both groups was normal, although with a statistically greater BMI from the normal group compared with sarcopenia (p < 0.001). Greater values and significant differences were found in step length and stride length from the normal elderly group (p < 0.01), and so was the length of the gait line and single support line (p < 0.05). Gait forward dynamics analysis results showed no motor neural or musculoskeletal disorders in their gait performance from the sarcopenia group. Conclusion: For the elderly, age did not largely affect the ALMI, BMI, or T-score, but BMI and ALMI were strongly correlated. In this study, significant differences were found in certain gait parameters between the elderly with sarcopenia and the normal elderly, which were related to absolute muscle strength, suggesting that sarcopenia was a disease mainly caused by decreased muscle mass. In addition, when abnormities were identified in step length, stride length, length of gait line, or length of single support line, it is proposed to take a DXA scan to confirm whether the elderly suffer from sarcopenia.

Outcomes of Genetic Testing-Based Cardiac Rehabilitation Program in Patients with Acute Myocardial Infarction after Percutaneous Coronary Intervention.

Objective: There can be extreme variability between individual responses to exercise training, and the identification of genetic variants associated with individual variabilities in exercise-related traits could guide individualized exercise programs. We aimed to screen the exercise-related gene sensitivity of patients with acute myocardial infarction after PCI by establishing the gene spectrum of aerobic exercise and cardiopulmonary function sensitivity, test the effect of individualized precision exercise therapy, and provide evidence for the establishment of a precision medicine program for clinical research. Methods: Aerobic exercise- and cardiopulmonary function-related genes and single-nucleotide polymorphisms (SNPs) were obtained by data mining utilizing a major publicly available biomedical repository, the NCBI PubMed database. Biological samples from all participants underwent DNA testing. We performed SNP detection using Samtools. A total of 122 patients who underwent PCI were enrolled in the study. We screened the first 24 cases with a high mutation frequency for aerobic exercise- and cardiopulmonary function-related genes and the last 24 cases with a low mutation frequency and separated them into two groups for the exercise intervention experiment. Results: In both the low mutation frequency group and the high mutation frequency group, after 8 weeks of exercise intervention, 6 MWT distance, 6 MWT%, VO2/kg at peak, and VO2/kg at AT were significantly improved, and the effect in the high mutation frequency group was significantly higher than that in the low mutation frequency group (6 MWT distance: 468 vs. 439, P=0.003; 6 MWT%: 85 vs. 77, P=0.002, VO2/kg at peak: 14.7 vs. 13.3, P=0.002; VO2/kg at AT: 11.9 vs. 13.3, P=0.003). Conclusions: There is extreme variability between individual responses to exercise training. The identification of genetic variants associated with individual variabilities in exercise-related traits could guide individualized exercise programs. We found that the subjects with a high mutation frequency in aerobic exercise and cardiopulmonary function-related genes achieved more cardiorespiratory fitness benefits in the aerobic exercise rehabilitation program and provided evidence for the establishment of a precision medicine program for clinical research.

The Metabolomic Characterization of Different Types of Coronary Atherosclerotic Heart Disease in Male.

Background: In clinical practice, many patients with coronary atherosclerotic heart disease (CAD) have atypical clinical symptoms. It is difficult to accurately identify stable CAD or unstable CAD early through clinical symptoms and coronary angiography. This study aimed to screen the potential metabolite biomarkers in male patients with stable CAD and unstable CAD. Methods: In this work, the metabolomic characterization of the male patients with healthy control (n = 42), stable coronary artery disease (n = 60), non-ST-elevation acute coronary syndrome (n = 45), including prepercutaneous corona intervention (n = 14), and postpercutaneous coronary intervention (n = 31) were performed by using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The serum samples of patients were analyzed by multivariate statistics. Results: Results showed that 17 altered metabolites were identified to have a clear distinction between the stable CAD group and the healthy subjects. Compared with the stable coronary artery disease group, 15 specific metabolite markers were found in the acute coronary syndrome group. The percutaneous coronary intervention also affected the metabolic behavior of patients with CAD. Conclusions: In summary, CAD is closely related to energy metabolism, lipid metabolism, and amino acid metabolism disorders. The different metabolic pattern characteristics of healthy, stable coronary artery disease and acute coronary syndrome are constructed, which brings a novel theoretical basis for the early diagnosis of patients with stable and unstable CAD.

Comprehensive Analysis of CRISPR-Cas9 Editing Outcomes in Yeast Xanthophyllomyces dendrorhous.

DNA repair after Cas9 cutting can result in deletions/insertions, genomic rearrangements, and rare nucleotide substitutions. However, most work has only focused on deletions/insertions resulting from repair after CRISPR-Cas9 action. Here, we comprehensively analyzed the editing outcomes induced by CRISPR-Cas9 treatment in yeast Xanthophyllomyces dendrorhous by Sanger and Illumina sequencing and identified diverse DNA repair patterns, including DNA deletions, interchromosomal translocations, and on-target nucleotide substitutions (point mutations). Some deletions were observed repeatedly, and others, especially large deletions, varied in size. Genome sequencing and structural variation analysis showed that the interchromosomal translocations happened between Cas9 target sites and the endogenous ADH4 promoter. In contrast to previous studies, analysis revealed that the on-target point mutations were not random. Importantly, these point mutations showed strong sequence dependence that is not consistent with previous work in Hela cells, where CRISPR-mediated substitutions were found to lack sequence dependence and conversion preferences. Finally, we found that the non-homologous end joining components Ku70, Ku80, Mre11, or RAD50, and the overlapping roles of non-essential DNA polymerases were necessary for the production of both point mutations and deletions. This work expands our knowledge of CRISPR-Cas9 mediated DNA repair.

Negative impacts of sea-level rise on soil microbial involvement in carbon metabolism.

Sea-level rise has been threatening the terrestrial ecosystem functioning of coastal islands, of which the most important component is carbon (C) cycling. However, metagenomic and metabolomic evidence documenting salt intrusion effects on molecular biological processes of C cycling are still lacking. Here, we investigated microbial communities, metagenomic taxonomy and function, and metabolomic profiles in the marine-terrestrial transition zone of low- and high-tide, and low- and high-land areas based on distances of 0 m, 50 m, 100 m, and 200 m, respectively, to the water-land junction of Neilingding Island. Our results showed that soil salinity (EC) was the dominant driver controlling bacterial abundance and community composition and metagenomic taxonomy and function. The metabolomic profiling at the low-tide site was significantly different from that of other sites. The low-tide site had greater abundance of Proteobacteria and Bacteroidetes (1.6-3.7 fold), especially Gammaproteobacteria, but lower abundance (62-83%) of Acidobacteria and Chloroflexi, compared with other three sites. The metagenomic functional genes related to carbohydrate metabolism decreased at the low-tide site by 15.2%, including the metabolism of aminosugars, di- and oligo-saccharides, glycoside hydrolases, and monosaccharides, leading to significant decreases in 21 soil metabolites, such as monosaccharide (l-gulose), disaccharide (sucrose and turanose), and oligosaccharides (stachyose and maltotetraose). Our study demonstrates that elevated salinity due to sea-level rise may suppress C-cycling genes and their metabolites, therefore having negative impacts on microbial metabolism of organic matter.

Secretome of Mesenchymal Stem Cells from Consecutive Hypoxic Cultures Promotes Resolution of Lung Inflammation by Reprogramming Anti-Inflammatory Macrophages.

The secretome from hypoxia-preconditioned mesenchymal stem cells (MSCs) has been shown to promote resolution of inflammation and alleviate acute lung injury (ALI) through its immunomodulatory function. However, the effects of consecutive hypoxic culture on immunomodulatory function of the MSCs secretome are largely unclarified. Here, we intend to investigate the effects of consecutive hypoxia on therapeutic efficacy of conditioned medium derived from MSCs (MSCs-CM) in alleviating ALI. Human umbilical cord-derived MSCs (UC-MSCs) were consecutively cultured in 21% O2 (Nor-MSCs) or in 1% O2 (Hypo-MSCs) from passage 0. Their conditioned medium (Nor-CM and Hypo-CM respectively) was collected and administered into ALI models. Our findings confirmed that Hypo-MSCs exhibited increased proliferation ability and decreased cell senescence compared with Nor-MSCs. Consecutive hypoxia promoted UC-MSCs to secrete immunomodulatory cytokines, such as insulin-like growth factor 1(IGF1), IL10, TNFα-stimulated gene 6(TSG6), TGFß, and prostaglandin E2 (PGE2). Both Nor-CM and Hypo-CM could effectively limit lung inflammation, promote efferocytosis and modulate anti-inflammatory polarization of lung macrophages in ALI models. Moreover, the effects of Hypo-CM were more potent than Nor-CM. Taken together, our findings indicate that consecutive hypoxic cultures could not only promote both proliferation and quality of UC-MSCs, but also enhance the therapeutic efficacy of their secretome in mitigating lung inflammation by promoting efferocytosis and anti-inflammatory polarization of macrophages.