Open conformation of tetraspanins shapes interaction partner networks on cell membranes.

Tetraspanins, including CD53 and CD81, regulate a multitude of cellular processes through organizing an interaction network on cell membranes. Here, we report the crystal structure of CD53 in an open conformation poised for partner interaction. The large extracellular domain (EC2) of CD53 protrudes away from the membrane surface and exposes a variable region, which is identified by hydrogen-deuterium exchange as the common interface for CD53 and CD81 to bind partners. The EC2 orientation in CD53 is supported by an extracellular loop (EC1). At the closed conformation of CD81, however, EC2 disengages from EC1 and rotates toward the membrane, thereby preventing partner interaction. Structural simulation shows that EC1-EC2 interaction also supports the open conformation of CD81. Disrupting this interaction in CD81 impairs the accurate glycosylation of its CD19 partner, the target for leukemia immunotherapies. Moreover, EC1 mutations in CD53 prevent the chemotaxis of pre-B cells toward a chemokine that supports B-cell trafficking and homing within the bone marrow, a major CD53 function identified here. Overall, an open conformation is required for tetraspanin-partner interactions to support myriad cellular processes.

Hydrological profile observation scheme based on optical fiber sensing for polar sea ice buoy monitoring.

The monitoring of hydrological elements in the polar region is the basis for the study of the dynamic environment under the ice. The traditional cross-season subglacial hydrological environment monitoring mainly relies on tether-type vertical profile measurement ice-based buoys, which have the advantages such as high reliability, high measurement accuracy, and real-time communication, while also has disadvantages of high-cost, large volume and weight, high power consumption, and complex layout. Therefore, it is urgent to develop a new type of ice-based profile buoy with low-cost, miniaturization, low power consumption, convenient deployment, and high reliability. In this paper, a novel optical fiber sensing scheme for ice-based buoy monitoring is proposed, which uses arrayed fiber grating to measure seawater temperature and depth profile and uses a dual-conduction mode resonance mechanism to measure seawater salinity. The temperature, depth, and salinity of seawater can be detected by an all-optical fiber technology in real-time. Preliminary experiments show that the temperature accuracy is ±0.1 °C in the range of -5∼35 °C, the salinity accuracy is ±0.03‰ in the range of 30‰âˆ¼40‰, and the vertical spatial resolution of depth can be adjusted in the range of 0∼1000 m, which can better meet the requirements of polar hydrological multi-layer profile observation. It can provide an innovative technology and equipment support for studying the spatiotemporal change process of the polar subglacial ocean.

Changes in Blood Pressure is Associated with Bone Loss in US Adults: A Cross-Sectional Study from NHANES 2005-2018.

Hypertension and osteoporosis are common geriatric diseases, sharing similar risk factors. This study aims to investigate this association and explore relatively mixed variables. Our study included 12,787 eligible participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Included participants had valid data on hypertension and osteoporosis, without tumors, liver diseases, gout or thyroid diseases. We explored the association between hypertension and osteoporosis by logistic regression and examined blood pressure and BMD/BMC by linear and non-linear regression. Moreover, we used machine learning models to predict the importance of various factors in the occurrence of osteoporosis and evaluated causality by mendelian randomization. Our study found that osteoporosis is significantly associated with hypertension [OR 2.072 (95% CI 2.067-2.077), p < 0.001]. After adjusting for co-variances, the association remained significant [OR 1.223 (95% CI 1.220-1.227), p < 0.001]. Our study showed that osteoporosis is positively associated with hypertension in the US population. A variety of factors influence this relationship. Specific regulatory mechanisms and confounding factors need to be further investigated.

A critical review of the central role of microbial regulation in the nitrogen biogeochemical process: New insights for controlling groundwater nitrogen contamination.

With the increase of nitrogen (N) input in vadose zones-groundwater systems, N contamination in groundwater has become a global environmental and geological issue that has a profound impact on the ecological environment and human health. N migration in the vadose zone is the most significant means of contaminating the groundwater aquifer. However, the current research on the control of groundwater N contamination focuses solely on the content change of certain indicators and is unable to comprehend the cause and subsequent development of groundwater N contamination. These factors pose significant environmental management challenges in areas where groundwater is contaminated with nitrate. In recent years, research on the migration and transformation behavior of various N forms in vadose zones-groundwater systems has yielded some breakthroughs but also encountered some roadblocks. The biogeochemical behavior of nitrogen consists of a series of intricate chain reaction cycles (called N-cycle). The crucial role of microorganisms in the N biogeochemical process has attracted the interest of soil carbon- and N-cycle researchers and become a hot topic of study. Nonetheless, the role of microbial regulation in groundwater systems has been largely neglected and needs to be summarized immediately. Consequently, this review summarizes recent advancements, mechanisms, and challenges, and proposes a dynamic perspective on microbial regulation. On the basis of these findings, we propose a dynamic and comprehensive groundwater N system centered on microbial regulation. In addition, we critically summarized the migration and transformation behavior of the most recent N indicators, the impact of global environmental change on each N component, and the non-negligible effects of these factors on the control of groundwater N contamination. Future research must focus on the migration and transformation behavior of nitrogen in the deep vadose zone, based on the dynamic regulation of microorganisms, and complete the missing pieces of the developed N-cycle index system. These are essential for providing scientific guidance for global N management and effectively mitigating N contamination in groundwater.

Metabolic pathway analysis of hyperuricaemia patients with hyperlipidaemia based on high-throughput mass spectrometry: a case‒control study.

BACKGROUND: Both hyperuricaemia and hyperlipidaemia are common metabolic diseases that are closely related to each other, and both are independent risk factors for the development of a variety of diseases. HUA combined with hyperlipidaemia increases the risk of nonalcoholic fatty liver disease and coronary heart disease. This study aimed to investigate the relationship between HUA and hyperlipidaemia and study the metabolic pathway changes in patients with HUA associated with hyperlipidaemia using metabolomics. METHODS: This was a case‒control study. The prevalence of hyperlipidaemia in HUA patients in the physical examination population of Tianjin Union Medical Centre in 2018 was investigated. Metabolomics analysis was performed on 308 HUA patients and 100 normal controls using Orbitrap mass spectrometry. A further metabolomics study of 30 asymptomatic HUA patients, 30 HUA patients with hyperlipidaemia, and 30 age-and sex-matched healthy controls was conducted. Differential metabolites were obtained from the three groups by orthogonal partial least-squares discrimination analysis, and relevant metabolic pathways changes were analysed using MetaboAnalyst 5.0 software. RESULTS: The prevalence of hyperlipidaemia in HUA patients was 69.3%. Metabolomic analysis found that compared with the control group, 33 differential metabolites, including arachidonic acid, alanine, aspartate, phenylalanine and tyrosine, were identified in asymptomatic HUA patients. Pathway analysis showed that these changes were mainly related to 3 metabolic pathways, including the alanine, aspartate and glutamate metabolism pathway. Thirty-eight differential metabolites, including linoleic acid, serine, glutamate, and tyrosine, were identified in HUA patients with hyperlipidaemia. Pathway analysis showed that they were mainly related to 7 metabolic pathways, including the linoleic acid metabolism pathway, phenylalanine, tyrosine and tryptophan biosynthesis pathway, and glycine, serine and threonine metabolism pathway. CONCLUSIONS: Compared to the general population, the HUA population had a higher incidence of hyperlipidaemia. HUA can cause hyperlipidaemia. by affecting the metabolic pathways of linoleic acid metabolism and alanine, aspartate and glutamate metabolism. Fatty liver is closely associated with changes in the biosynthesis pathway of pahenylalanine, tyrosine, and tryptophan in HUA patients with hyperlipidaemia. Changes in the glycine, serine and threonine metabolism pathway in HUA patients with hyperlipidaemia may lead to chronic kidney disease.

Footprinting Mass Spectrometry of Membrane Proteins: Ferroportin Reconstituted in Saposin A Picodiscs.

Membrane proteins participate in a broad range of cellular processes and represent more than 60% of drug targets. One approach to their structural analyses is mass spectrometry (MS)-based footprinting including hydrogen/deuterium exchange (HDX), fast photochemical oxidation of proteins (FPOP), and residue-specific chemical modification. Studying membrane proteins usually requires their isolation from the native lipid environment, after which they often become unstable. To overcome this problem, we are pursuing a novel methodology of incorporating membrane proteins into saposin A picodiscs for MS footprinting. We apply different footprinting approaches to a model membrane protein, mouse ferroportin, in picodiscs and achieve high coverage that enables the analysis of the ferroportin structure. FPOP footprinting shows extensive labeling of the extramembrane regions of ferroportin and protection at its transmembrane regions, suggesting that the membrane folding of ferroportin is maintained throughout the labeling process. In contrast, an amphipathic reagent, N-ethylmaleimide (NEM), efficiently labels cysteine residues in both extramembrane and transmembrane regions, thereby affording complementary footprinting coverage. Finally, optimization of sample treatment gives a peptic-map of ferroportin in picodiscs with 92% sequence coverage, setting the stage for HDX. These results, taken together, show that picodiscs are a new platform broadly applicable to mass spectrometry studies of membrane proteins.

Strained Endotaxial PbS Nanoprecipitates Boosting Ultrahigh Thermoelectric Quality Factor in n-Type PbTe As-Cast Ingots.

Lead telluride (PbTe) has long been regarded as an excellent thermoelectric material at intermediate temperature range (573-873 K); however, n-type PbTe's performance is always relatively inferior to its p-type counterpart mainly due to their different electronic band structures. In this work, an ultrahigh thermoelectric quality factor (µ/κL  ≈ 1.36 × 105 cm3 KJ-1 V-1 ) is reported in extra 0.3% Cu doped n-type (PbTe)0.9 (PbS)0.1 as-cast ingots. Transmission electron microscopy (TEM) characterization reveals that excess PbS exists in PbTe matrix as strained endotaxial nanoprecipitates, which affect electrical and thermal conduction discriminately: (1) coherent PbTe/PbS lattice minimizes the interface scattering of charge carriers; (2) periodic strain centers at PbTe/PbS interface exhibit intensive strain contrast, which can strongly scatter heat-carrying phonons. Electron backscattered diffraction (EBSD) characterization illustrates very large PbTe grains (≈1 mm) in these as-cast ingots, ensuring an extremely low grain boundary scattering rate thus a very high charge carrier mobility. Eventually, a remarkably high ZTmax  ≈ 1.5 at 773 K and an outstanding ZTavg  ≈ 1.0 between 323 and 773 K are simultaneously achieved in the (PbTe)0.9 (PbS)0.1  +0.3%Cu sample; these values are highly competitive with reported state-of-art n-type PbTe materials.

Glucose metabolic disorder in Klinefelter syndrome: a retrospective analysis in a single Chinese hospital and literature review.

BACKGROUND: We aimed to investigate the clinical characteristics and islet ß-cell function in patients with Klinefelter syndrome (KS) and hyperglycemia. METHODS: This is a retrospective study. In total, 22 patients diagnosed with KS were identified from the electronic medical record system, including 9 patients with hyperglycemia (total patients with hyperglycemia, THG-KS group) and 5 hyperglycemic KS patients with oral glucose tolerance test (OGTT) results (HG-KS group). An additional 5 subjects with hyperglycemia and 5 normal glucose tolerance (NGT) subjects matched based on body mass index were included as the HG group and NGT group, respectively. Data from clinical and laboratory examinations were collected. We further performed a literature review of KS and hyperglycemia. RESULTS: We found that KS patients developed abnormal glucose metabolism earlier in life than those without KS, and the median age was 17 years, ranging from 10 years to 19 years. Six of 17 (35.3%) patients were diagnosed with diabetes mellitus and 3 of 17 (17.6%) patients were diagnosed with prediabetes. Among 10 patients with both fasting blood glucose and insulin results recorded, there were 8 out of 17 (47.1%) KS patients had insulin resistance. The prevalence of hypertension and dyslipidemia was higher in patients with hyperglycemia and KS than in patients with NGT KS. Compared with the HG group, insulin sensitivity levels were lower in HG-KS group, whereas homeostasis model assessment of ß-cell function levels (p = 0.047) were significantly, indicating higher insulin secretion levels in the HG-KS group. CONCLUSIONS: KS patients develop hyperglycemia earlier in life than those without KS and show lower insulin sensitivity and higher insulin secretion. These patients also have a higher prevalence of other metabolic diseases and may have different frequencies of developing KS-related symptoms.

BAG3-Related Myofibrillar Myopathy Presenting as Hypercapnia: A Case Report and Literature Review.

Objective BAG3-related myopathy is a rare condition so far reported in twenty patients worldwide. The purpose of this study was to draw attention to this rare disease and to the fact that BAG3-related myopathy should be considered as a rare differential diagnosis of hypercapnia. Methods We report a sporadic case of a 14-year-old Chinese girl with a de novo p.Pro209Leu mutation in BAG3 and reviewed the literatures for reported cases related to this mutation. Results We described a 14-year-old Chinese girl who presented with gradually appearing symptoms of hypercapnia that required assisted ventilation. The muscle biopsy and the blood whole-exome sequencing results confirmed the diagnosis of myofibrillar myopathy with a de novo p.Pro209Leu mutation in BAG3. Totally twenty-one patients from twenty families with a confirmed diagnosis of BAG3-related myopathy were reported to date, including this patient and literature review. The male to female ratio was 11:10 and most showed initial symptoms in the first decade of life. Most patients presented toe/clumsy walking or running as the onset symptom, followed by muscle weakness or atrophy. Creatine kinase levels were elevated in fourteen patients and were normal in three. Eighteen patients developed respiratory insufficiency during the disease course and thirteen (one could not tolerate non-invasive assisted ventilation) required non-invasive assisted ventilation for treatment. Except for one not reported, heart involvement was found in seventeen patients during the disease course and seven underwent heart transplantation. Z-disk streaming and aggregation could be observed in most of the patients' muscle histology. In the long-term follow-up, five patients died of cardiac or respiratory failure. Conclusion BAG3-associated myopathy is a rare type of myofibrillar myopathy. It should be considered as a rare differential diagnosis of hypercapnia.

Membrane Protein Structure in Live Cells: Methodology for Studying Drug Interaction by Mass Spectrometry-Based Footprinting.

Mass spectrometry-based footprinting is an emerging approach for studying protein structure. Because integral membrane proteins are difficult targets for conventional structural biology, we recently developed a mass spectrometry (MS) footprinting method to probe membrane protein-drug interactions in live cells. This method can detect structural differences between apo and drug-bound states of membrane proteins, with the changes inferred from MS quantification of the cysteine modification pattern, generated by residue-specific chemical labeling. Here, we describe the experimental design, interpretation, advantages, and limitations of using cysteine footprinting by taking as an example the interaction of warfarin with vitamin K epoxide reductase, a human membrane protein. Compared with other structural methods, footprinting of proteins in live cells produces structural information for the near native state. Knowledge of cellular conformational states is a necessary complement to the high-resolution structures obtained from purified proteins in vitro. Thus, the MS footprinting method is broadly applicable in membrane protein biology. Future directions include probing flexible motions of membrane proteins and their interaction interface in live cells, which are often beyond the reach of conventional structural methods.

Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB.

The Origin Recognition Complex (ORC) is a six-subunit protein important for the initiation of DNA replication in eukaryotic cells. Orc6 is the smallest and the least conserved among ORC subunits. It is required for the DNA replication but also has a function in cytokinesis in metazoan species, however, the mechanisms of Orc6 action in these processes are not clear. Here we report a structure of the middle domain of human Orc6. This domain has an overall fold similar to the corresponding helical domain of transcription factor TFIIB. Based on these findings, a model of Orc6 binding to DNA is produced. We have identified amino acids of Orc6 which are directly involved in DNA binding. Alterations of these amino acids abolish DNA binding ability of Orc6 and also result in reduced levels of DNA replication in vitro and in cultured cells. Our data indicate that Orc6 is one of the DNA binding subunits of ORC in metazoan species. We propose that Orc6 may participate in positioning of ORC at the origins of DNA replication similar to the role of TFIIB in positioning transcription preinitiation complex at the promoter.

Topical delivery of drugs in the treatment of high-grade cervical squamous intraepithelial lesions: A meta-analysis.

OBJECTIVE: The present study aims to evaluate the efficacy and effect of localized delivery of drugs in the treatment of high-grade squamous intraepithelial lesion (HSIL) based on a meta-analysis. STUDY DESIGN: Databases including Cochrane Library, PubMed, Embase, Scopus, CNKI, and Wanfang were searched from their inception till August 2022. Randomized controlled trials (RCTs) that compared the efficacy of drugs and surgery in the treatment of HSIL were collected. A meta-analysis was performed using the software of Review Manager (version 5.4.1). RESULTS: Eight RCTs involving 523 patients were included in the meta-analysis. For HSIL, the rate of cervical lesions histological regression was 69.85 % in the surgery group and 59.88 % in the drug group, there was no significant difference between the two groups [OR = 0.45, 95 % CI (0.07, 3.03), P = 0.41]. The histological regression rate of cervical lesions in the placebo group was 37.76 %, and the difference between the drug group and the placebo group was statistically significant [OR = 4.94, 95 % CI (2.65, 9.20), P < 0.00001]. CONCLUSION: A total of four drugs were involved in the eight RCTS included in this study, which were imiquimod, 5-fluorouracil (5-FU), cidofovir and interferon. The results showed that although drug administration was effective in the histological regression of HSIL, the efficacy was less than about 10% of surgical treatment. Considering the recurrence of the disease after surgery and the problems of abortion, premature delivery and premature rupture of membranes after cervical conization in reproductive women, drug therapy can be used as a supplement to surgery or conservative treatment to promote the histological regression of cervical lesions in patients with HSIL.

Effect of Sympathetic Blockade on Spontaneous Discharge and the H-Reflex at Myofascial Trigger Points in Rats.

Purpose: Myofascial trigger points (MTrPs) are the main cause of myofascial pain syndrome (MPS), and patients with MPS also have symptoms of sympathetic abnormalities. Consequently, this study aimed to investigate the potential relationship between MTrPs and sympathetic nerves. Materials and Methods: Twenty-four seven-week-old male rats were randomly divided into four groups (six rats every group). Groups I and II were kept in normal condition (n=12), and groups III and IV underwent MTrPs modelling (n=12). After successful MTrPs modelling, differences in sympathetic outcomes between the MTrPs groups (III and IV) and non-MTrPs groups (I and II) were observed. Sympathetic blockade was then applied to groups III and I (n=12). Data were collected on peak inversion spontaneous potentials (PISPs) and the H-reflex-evoked electromyography during spontaneous discharge at the MTrPs before and after sympathetic blockade. Results: Systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate were significantly higher in the MTrPs group than in the non-MTrPs group (P<0.05). Compared with group I, group III had the PISPs potential lower wave amplitude, shorter duration and amplitude-to-duration ratio, and lower H latency and latency difference H-M (P<0.05). Compared with group IV, group III had the PISPs potential lower wave amplitude, duration, amplitude-to-duration ratio, M-wave latency, H maximum wave amplitude, and maximal wave amplitude ratio H/M (P<0.05). The changes before and after sympathetic blockade in the MTrPs group were significant, and the amplitude, duration, and amplitude-to-duration ratio of the PISPs potentials were lower after the blockade (P<0.05). Conclusion: MTrPs and sympathetic nerves interact with each other forming a specific relationship. MTrPs sensitize sympathetic nerves, and sympathetic nerve abnormalities affect local muscle myoelectric hyperactivity, leading to MTrPs. This finding is instructive for the clinical management of sympathetic disorders.

The key role of muscle spindles in the pathogenesis of myofascial trigger points according to ramp-and-hold stretch and drug intervention in a rat model.

This study investigated whether abnormal peak inversion spontaneous potentials (PISPs) recorded at resting myofascial trigger points (MTrPs) stem from the discharge of muscle spindles. Forty-eight male Sprague-Dawley rats were randomly divided into six groups. Five groups underwent MTrP modeling intervention, whereas one group did not receive intervention and was duly designated as the blank control. After model construction, five rat models were randomly subjected to ramp-and-hold stretch tests, succinylcholine injection, eperisone hydrochloride injection, saline injection, and blank drug intervention. By contrast, the rats in the blank control group were subjected to ramp-and-hold stretch tests as a control. Frequencies and amplitudes of PISPs were recorded pre- and post-interventions and compared with those of the blank group. Stretch tests showed that the depolarization time and amplitude of PISPs ranged from 0.4 ms to 0.9 ms and from 80 uV to 140 µV, respectively. However, no PISPs were observed in the control rats. The frequency of PISPs in the ramp and hold phases and the first second after the hold phase was higher than that before stretching (p < 0.01). Succinylcholine and eperisone exerted excitatory and inhibitory effects on PISPs, respectively. In the group injected with 0.9% saline, no considerable differences of the PISPs were observed during the entire observation period. In conclusion, PISPs recorded at resting MTrPs are closely related to muscle spindles. The formation of MTrPs may be an important factor that regulate dysfunctional muscle spindles.

Inductive Meta-path Learning for Schema-complex Heterogeneous Information Networks.

Heterogeneous Information Networks (HINs) are information networks with multiple types of nodes and edges. The concept of meta-path, i.e., a sequence of entity types and relation types connecting two entities, is proposed to provide the meta-level explainable semantics for various HIN tasks. Traditionally, meta-paths are primarily used for schema-simple HINs, e.g., bibliographic networks with only a few entity types, where meta-paths are often enumerated with domain knowledge. However, the adoption of meta-paths for schema-complex HINs, such as knowledge bases (KBs) with hundreds of entity and relation types, has been limited due to the computational complexity associated with meta-path enumeration. Additionally, effectively assessing meta-paths requires enumerating relevant path instances, which adds further complexity to the meta-path learning process. To address these challenges, we propose SchemaWalk, an inductive meta-path learning framework for schema-complex HINs. We represent meta-paths with schema-level representations to support the learning of the scores of meta-paths for varying relations, mitigating the need of exhaustive path instance enumeration for each relation. Further, we design a reinforcement-learning based path-finding agent, which directly navigates the network schema (i.e., schema graph) to learn policies for establishing meta-paths with high coverage and confidence for multiple relations. Extensive experiments on real data sets demonstrate the effectiveness of our proposed paradigm.

Tailoring local chemical fluctuation of high-entropy structures in thermoelectric materials.

In high-entropy materials, local chemical fluctuation from multiple elements inhabiting the same crystallographic site plays a crucial role in their unique properties. Using atomic-resolution chemical mapping, we identified the respective contributions of different element characteristics on the local chemical fluctuation of high-entropy structures in thermoelectric materials. Electronegativity and mass had a comparable influence on the fluctuations of constituent elements, while the radius made a slight contribution. The local chemical fluctuation was further tailored by selecting specific elements to induce large lattice distortion and strong strain fluctuation to lower lattice thermal conductivity independent of increased entropy. The chemical bond fluctuation induced by the electronegativity difference had a noticeable contribution to the composition-dependent lattice thermal conductivity in addition to the known fluctuations of mass and strain field. Our findings provide a fundamental principle for tuning local chemical fluctuation and lattice thermal conductivity in high-entropy thermoelectric materials.

Metformin-induced changes of the gut microbiota in patients with type 2 diabetes mellitus: results from a prospective cohort study.

BACKGROUND: The influence of the microbiota on hypoglycemic agents is becoming more apparent. The effects of metformin, a primary anti-diabetes drug, on gut microbiota are still not fully understood. RESEARCH DESIGN AND METHODS: This prospective cohort study aims to investigate the longitudinal effects of metformin on the gut microbiota of 25 treatment-naïve diabetes patients, each receiving a daily dose of 1500 mg. Microbiota compositions were analyzed at baseline, and at 1, 3, and 6 months of medication using 16S rRNA gene sequencing. RESULTS: Prior to the 3-month period of metformin treatment, significant improvements were noted in body mass index (BMI) and glycemic-related parameters, such as fasting blood glucose (FPG) and hemoglobin A1c (HbA1c), alongside homeostasis model assessment indices of insulin resistance (HOMA-IR). At the 3-month mark of medication, a significant reduction in the α-diversity of the gut microbiota was noted, while ß-diversity exhibited no marked variances throughout the treatment duration. The Firmicutes to Bacteroidetes ratio. markedly decreased. Metformin treatment consistently increased Escherichia-Shigella and decreased Romboutsia, while Pseudomonas decreased at 3 months. Fuzzy c-means clustering identified three longitudinal trajectory clusters for microbial fluctuations: (i) genera temporarily changing, (ii) genera continuing to decrease (Bacteroides), and (iii) genera continuing to increase(Lachnospiraceae ND3007 group, [Eubacterium] xylanophilum group, Romboutsia, Faecalibacterium and Ruminococcaceae UCG-014). The correlation matrix revealed associations between specific fecal taxa and metformin-related clinical parameters HbA1c, FPG, Uric Acid (UA), high-density lipoproteincholesterol (HDL-C), alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), triglyceride (TG) (P < 0.05). Metacyc database showed that metformin significantly altered 17 functional pathways. Amino acid metabolism pathways such as isoleucine biosynthesis predominated in the post-treatment group. CONCLUSIONS: Metformin's role in glucose metabolism regulation may primarily involve specific alterations in certain gut microbial species rather than an overall increase in microbial species diversity. This may suggest gut microbiota targets in future studies on metabolic abnormalities caused by metformin.

An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome.

Hormones mediate long-range cell communication and play vital roles in physiology, metabolism, and health. Traditionally, endocrinologists have focused on one hormone or organ system at a time. Yet, hormone signaling by its very nature connects cells of different organs and involves crosstalk of different hormones. Here, we leverage the organism-wide single cell transcriptional atlas of a non-human primate, the mouse lemur (Microcebus murinus), to systematically map source and target cells for 84 classes of hormones. This work uncovers previously-uncharacterized sites of hormone regulation, and shows that the hormonal signaling network is densely connected, decentralized, and rich in feedback loops. Evolutionary comparisons of hormonal genes and their expression patterns show that mouse lemur better models human hormonal signaling than mouse, at both the genomic and transcriptomic levels, and reveal primate-specific rewiring of hormone-producing/target cells. This work complements the scale and resolution of classical endocrine studies and sheds light on primate hormone regulation.