An improved diagnostic method for taurodontism and a comparative study on its effectiveness evaluation.

OBJECTIVE: The two commonly used diagnostic methods for taurodontism are susceptible to aging changes, mastication wear and other factors. Therefore, this study proposed an improved diagnostic method for taurodontism, and compared it with the previous two methods as a supplement for taurodontism diagnosis. METHODS: The included patients were aged 10-89 years and admitted to the Department of Stomatology of Hebei Eye Hospital from June 1, 2022 to May 31, 2023. Eighty cone-beam computed tomography images were divided equally into 4 groups: 10-29, 30-49, 50-69, and 70-89 years old. The right mandibular first molars were selected as measurement objects. Firstly, |BD| and taurodontism index (TI)-related parameters were measured using Shifman and Chanannel's method and crown-body(CB) and root (R) lengths was measured by Seow and Lai's method. The improved method used the length from the cementoenamel junction(CEJ) to the root bifurcation point(body, B)and the root length(root, R)as the measurement objects. Finally, TI, CB/R ratios, and B/R ratios were calculated according to the formulas given below. One-way ANOVA analysis was mainly used to compare the differences in the values, indices and ratios of taurodontism among different age groups (p<0.05). RESULTS: With the increase of age, |BD| and TI values decreased significantly (p<0.01). The CB/R ratios of 70-89 years group were significantly lower than those of the other three groups (p<0.01). Ratios derived from the improved method were significantly lower in the 70-89 years than in 10-29 years group (p<0.05). CONCLUSIONS: The |BD| and TI parameters proposed by Shifman and channel are significantly influenced by age. The measurements of Seow and Lai (CB/R ratios) were less affected by age compared with those of the former. The improved method(B/R ratios) was least affected by age, which would reduce error and bias in the measurement of taurodontism and obtain more objective results in older patients.

Transferrin receptor levels and its rare variant are associated with human obesity.

AIM: Iron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat development and functionality. However, whether TFRC levels and variants are associated with human obesity is unknown. METHODS: To investigate the association of TFRC levels and variants with human obesity, fat biopsies were obtained from surgery. Exon-sequencing and genetic assessments were conducted of a case-control study. For TFRC levels assessment in fat biopsy, 9 overweight and 12 lean subjects were involved. For genetic study, obese (n = 1271) and lean subjects (n = 1455) were involved. TFRC levels were compared in abdominal mesenteric fat of pheochromocytoma patients versus control subjects, and overweight versus lean subjects. For genetic study, whole-exome sequencing of obese and matched control subjects were conducted and analyzed. In addition, the possible disruption in protein stability of TFRC variant was assessed by structural and molecular analysis. RESULTS: TFRC levels are increased in human browning adipose tissue and decreased in fat of overweight patients. Besides, TFRC levels are negatively correlated with body mass index and positively correlated with uncoupling protein 1 levels. Furthermore, a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in obese subjects. Structural and functional study reveals impaired protein stability of the TFRC variant compared to wild-type. CONCLUSIONS: Reduced TFRC levels and its rare variant p.I337V with protein instability are associated with human obesity.

Physicochemical and biological changes on naturally aged microplastic surfaces in real environments over 10 months.

Microplastics (MPs) undergo aging over time, which can influence their behavior in the environment. While laboratory-simulated studies have investigated MP aging, research on natural aging in various real environments remains limited. This study aims to investigate the physical, chemical and biological changes that occur in five types of MPs after more than 10 months of natural aging in three different real environments: seawater, air and soil. Results are compared with previous laboratory experiments. The surface roughness of all types of aged MPs was found to be higher in seawater than in air and soil, which differed from previous simulated studies that showed the highest roughness in air. All aged MPs exhibited the occurrence of hydroxyl and carbonyl groups due to the oxidation processes. Interestingly, the MPs aged in soil showed the lowest level of these functional groups, while in seawater or air, some MPs demonstrated the highest. This contrasts with previous studies indicating the highest level of oxygen-containing functional groups in aged MPs in air. Bacterial analysis identified fourteen bacterial phyla on the surface of aged MPs in all three real environments, with varying abundance in specific environments. Notably, the composition of bacterial communities in the microplastisphere was determined by the surrounding environments, independent of MP types. Natural aging is more complex than laboratory simulations, and the degree of MP aging increases with the complexity of environmental factors. These findings enhance our understanding of the natural aging of MPs in different real environments.

Spatially Patterned, Porous Protein Crystals as Multifunctional Materials.

While the primary use of protein crystals has historically been in crystallographic structure determination, they have recently emerged as promising materials with many advantageous properties such as high porosity, biocompatibility, stability, structural and functional versatility, and genetic/chemical tailorability. Here, we report that the utility of protein crystals as functional materials can be further augmented through their spatial patterning and control of their morphologies. To this end, we took advantage of the chemically and kinetically controllable nature of ferritin self-assembly and constructed core-shell crystals with chemically distinct domains, tunable structural patterns, and morphologies. The spatial organization within ferritin crystals enabled the generation of patterned, multi-enzyme frameworks with cooperative catalytic behavior. We further exploited the differential growth kinetics of ferritin crystal facets to assemble Janus-type architectures with an anisotropic arrangement of chemically distinct domains. These examples represent a step toward using protein crystals as reaction vessels for complex multi-step reactions and broadening their utility as functional, solid-state materials. Our results demonstrate that morphology control and spatial patterning, which are key concepts in materials science and nanotechnology, can also be applied for engineering protein crystals.

Risk factors for the development of postpartum depression in individuals who screened positive for antenatal depression.

BACKGROUND: Women with antenatal depression often have a higher risk of developing postpartum depression (PPD) after delivery. A number of factors associated with the PDD in those previously reporting antenatal depression have been suggested, but further research is needed. This study aimed to investigate factors associated with developing subsequent postnatal depression in women who had screened positive for antenatal depression. METHODS: This study was carried out in Hangzhou women's Hospital. 578 women who experienced antenatal depression from this cohort were enrolled in this study. The sociodemographic and clinical characteristics of the participants were collected and tabulated against the incidence of postnatal depression. Binary logistic regression was used to estimate the effects of the principal underlying variables. The Chinese-version Edinburgh Postnatal Depression Scale (EPDS) was used to screen for PPD. Antenatal screening for depression was conducted at 28-34 weeks during pregnancy and postpartum depressive symptoms were assessed at 6 weeks after childbirth in the women. Path Analysis of Structural Equation Model (SEM) was employed to explore the direct, indirect, and total effects of risk factors of PPD. RESULTS: 57.6% (n = 333) of the participants subsequently developed PPD in our study. The results of the logistic analysis indicated that ages ≤ 35 years old (OR = 1.852; 95%CI: 1.002-3.423), non-one-child families (OR = 1.518; 95%CI: 1.047-2.200), and rare care from partner during pregnancy (OR = 2.801; 95%CI: 1.038-7.562), the antenatal EPDS score (OR = 1.128; 95%CI: 1.052-1.209), pyrexia during pregnancy (OR = 2.43; 95%CI: 1.358-4.345), fairly good (OR = 1.836; 95%CI: 1.009-3.340), fairly bad (OR = 3.919; 95%CI:2.072-7.414) and very bad postpartum sleep quality (OR = 9.18; 95%CI: 2.335-36.241) were associated with increased risk of PPD (compared to very good postpartum sleep quality). In path analysis model, antenatal EPDS score (standardized total ß = 0.173) and pyrexia during pregnancy (standardized total ß = 0.132) had both direct and indirect effects (the impact on outcome variables needs to be determined through other variables) on PPD. Sleep quality after delivery (standardized ß = 0.226) and one-child family (standardized ß = 0.088) had direct effects only on PPD. CONCLUSION: The results from our study indicated that more than 50% of the women who experienced antepartum depression would subsequently develop PPD. Depressive symptoms and pyrexia during pregnancy increase PPD scores, and these effects were in part mediated via poor sleep quality during the postpartum period.

The rs1421085 variant within FTO promotes brown fat thermogenesis.

One lead genetic risk signal of obesity-the rs1421085 T>C variant within the FTO gene-is reported to be functional in vitro but lacks evidence at an organism level. Here we recapitulate the homologous human variant in mice with global and brown adipocyte-specific variant knock-in and reveal that mice carrying the C-allele show increased brown fat thermogenic capacity and resistance to high-fat diet-induced adiposity, whereas the obesity-related phenotypic changes are blunted at thermoneutrality. Both in vivo and in vitro data reveal that the C-allele in brown adipocytes enhances the transcription of the Fto gene, which is associated with stronger chromatin looping linking the enhancer region and Fto promoter. Moreover, FTO knockdown or inhibition effectively eliminates the increased thermogenic ability of brown adipocytes carrying the C-allele. Taken together, these findings identify rs1421085 T>C as a functional variant promoting brown fat thermogenesis.

Human RSPO1 Mutation Represses Beige Adipocyte Thermogenesis and Contributes to Diet-Induced Adiposity.

Recent genetic evidence has linked WNT downstream mutations to fat distribution. However, the roles of WNTs in human obesity remain unclear. Here, the authors screen all Wnt-related paracrine factors in 1994 obese cases and 2161 controls using whole-exome sequencing (WES) and identify that 12 obese patients harbor the same mutations in RSPO1 (p.R219W/Q) predisposing to human obesity. RSPO1 is predominantly expressed in visceral fat, primarily in the fibroblast cluster, and is increased with adiposity. Mice overexpressing human RSPO1 in adipose tissues develop obesity under a high-fat diet (HFD) due to reduced brown/beige fat thermogenesis. In contrast, Rspo1 ablation resists HFD-induced adiposity by increasing thermogenesis. Mechanistically, RSPO1 overexpression or administration significantly inhibits adipocyte mitochondrial respiration and thermogenesis via LGR4-Wnt/ß-catenin signaling pathway. Importantly, humanized knockin mice carrying the hotspot mutation (p.R219W) display suppressed thermogenesis and recapitulate the adiposity feature of obese carriers. The mutation disrupts RSPO1's electrostatic interaction with the extracellular matrix, leading to excessive RSPO1 release that activates LGR4-Wnt/ß-catenin signaling and attenuates thermogenic capacity in differentiated beige adipocytes. Therefore, these findings identify that gain-of-function mutations and excessive expression of RSPO1, acting as a paracrine Wnt activator, suppress fat thermogenesis and contribute to obesity in humans.

High prevalence of taurodontism in North China and its relevant factors: a retrospective cohort study.

OBJECTIVE: The purpose of this study was to investigate the prevalence and relevant factors of taurodontism in North China. METHODS: We retrospectively analysed the cone beam computed tomography (CBCT) of 1025 patients (496 male and 529 female) aged between 10 and 59 years. The crown-body/root (CB/R) ratios of the maxillary and mandibular molars were measured. The prevalence of hypotaurodontism, mesotaurodontism, and hypertaurodontism was then calculated and the incidence of taurodontism along with its relevant factors, was evaluated. RESULTS: The overall rate of taurodontism in North China was as high as 78.9%. If the third molars (opsigenes) were excluded, which have a big morphological variation from each other, the rate was 52.4%. The mean CB/R ratio of taurodontism differs from tooth position: maxillary mandibular third molars > maxillary third molars > maxillary second molars > maxillary first molars > mandibular second molars > mandibular first molars (P < 0.05). In addition, the 1025 patients were divided into different age groups, and it was found that the mean CB/R ratio decreased with age (P < 0.05). Moreover, the CB/R ratio of the mandibular first and second molars in female patients was higher than males (P < 0.05). CONCLUSION: This study revealed that taurodontism is widely prevalent in North China. The incidence of taurodontism increases the closer the tooth is to the back end of the dental arch, and quite a few of the maxillary and mandibular third molars teeth have tapered roots. And the taurodontism is decreased by age, as there were more affected female than male patients.

Association between antenatal depression and adverse perinatal outcomes: a prospective cohort study.

BACKGROUND: Antenatal depression might cause adverse pregnancy outcomes. However, previous study results were inconsistent, especially in the low- and middle- income countries. We aimed to study the association between antenatal depression and adverse perinatal outcomes in a Chinese population. METHODS: We performed a prospective cohort study and enrolled pregnant women from January 2020 to January 2021. Antenatal depressive symptoms in the third trimester of pregnancy were evaluated by the Edinburgh Postpartum Depression Scale (EPDS). Baseline characteristics and pregnancy outcomes were recorded. After adjusting for confounding factors (age, occupation, education level, and annual income), multivariate logistic regression analysis was applied to evaluate the associations between antenatal depression and pregnancy outcomes. RESULTS: Among the 5209 participants, 1448 (27.7 %) pregnant women were positive for depression. After adjusting for potential confounders, women with antenatal depressive symptoms were significantly more likely to deliver prematurely [Odds ratio (OR) = 1.404, 95 % confidence interval (CI) = 1.020-1.933, P = 0.037] and receive cesarean section (OR = 1.154, 95 % CI = 1.002-1.331, P = 0.048). LIMITATIONS: EPDS, not a structured diagnostic interview, was used for psychological assessment. In addition, we only screened the women in their third trimester in a single research center. The association between the duration of antenatal depression and perinatal outcomes was not evaluated. CONCLUSIONS: Depressive symptoms were common among Chinese women in their third trimester of pregnancy. Women with antenatal depressive symptoms had increased cesarean section and preterm delivery risks. Screening and treatment for antenatal depression are needed during the prenatal care.

Integrating UPLC-HR-MS/MS, Network Pharmacology, and Experimental Validation to Uncover the Mechanisms of Jin'gan Capsules against Breast Cancer.

In the theory of traditional Chinese medicine (TCM), "liver-qi" stagnation and heat-induced toxicity represent the main etiologies of breast cancer. Recently, several TCMs with heat-clearing and detoxification efficacy have shown inhibitory effects on breast cancer. Jin'gan capsules (JGCs), initially approved to treat colds in China, are a heat-clearing and detoxification TCM formula. However, the anticancer activity of JGCs against breast cancer and its underlying mechanisms remain unclear. First, we assessed the antiproliferative activity of JGCs in breast cancer cell lines and evaluated their effects on cell apoptosis and the cell cycle by flow cytometry. Furthermore, we identified the potential bioactive components of JGCs and their corresponding target genes and constructed a bioactive compound-target interaction network by ultra-performance liquid chromatography-high-resolution tandem mass spectrometry (UPLC-HR-MS/MS) and network pharmacology analysis. Finally, the underlying mechanism was investigated through gene function enrichment analysis and experimental validation. We found that JGCs significantly inhibited breast cancer cell growth with IC50 values of 0.56 ± 0.03, 0.16 ± 0.03, and 0.94 ± 0.09 mg/mL for MDA-MB-231, MDA-MB-468, and MCF-7, respectively. In addition, JGC treatment dramatically induced apoptosis and S phase cell cycle arrest in breast cancer cells. Western blot analysis confirmed that JGCs could regulate the protein levels of apoptosis- and cell cycle-related genes. Utilizing UPLC-HR-MS/MS analysis and network pharmacology, we identified 7 potential bioactive ingredients in JGCs and 116 antibreast cancer targets. Functional enrichment analysis indicated that the antitumor effects of JGCs were strongly associated with apoptosis and the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. Western blot analysis validated that JGC treatment markedly decreased the expression levels of p-JAK2, p-STAT3, and STAT3. Our findings suggest that JGCs suppress breast cancer cell proliferation and induce cell cycle arrest and apoptosis partly by inhibiting the JAK2/STAT3 signaling pathway, highlighting JGCs as a potential therapeutic candidate against breast cancer.

Establishment of an Ex Vivo Tissue Culture Model for Evaluation of Antitumor Efficacy in Clear Cell Renal Cell Carcinoma.

There are many potential immunotherapeutic targets for cancer immunotherapy, which should be assessed for efficacy before they enter clinical trials. Here we established an ex vivo cultured patient-derived tumor tissue model to evaluate antitumor effectiveness of one VISTA inhibitor, given that our previous study showed that VISTA was selectively highly expressed in human clear cell renal cell carcinoma (ccRCC) tumors. We observed that all the tested patients responded to the anti-VISTA monoclonal antibody as manifested by TNF-α production, but only a small fraction were responders to the anti-PD-1 antibody. Co-blockade of VISTA and PD-1 resulted in a synergistic effect in 20% of RCC patients. Taken together, these findings indicate that this ex vivo tumor slice culture model represents a viable tool to evaluate antitumor efficacies for the inhibitors of immune checkpoints and further supports that VISTA could serve as a promising target for immunotherapy in ccRCC.

GREM2 is associated with human central obesity and inhibits visceral preadipocyte browning.

BACKGROUND: Some circulating proteins are linked to central adiposity. Gremlin 2 (GREM2) functions as a secreted factor involved in osteogenesis and adipogenesis. Here, we investigated the association of blood GREM2 levels and central adiposity, and the biological roles of GREM2 in the browning program of visceral preadipocytes. METHODS: Three independent cohorts were applied to detect circulating GREM2 levels. Recombinant Grem2 protein, Grem2 overexpression and knockout mouse models, and preadipocyte-specific Bmpr2 knockout mice were used to assess the roles of Grem2 in the browning program. FINDINGS: We detected the presence of GREM2 protein in human serum using an ELISA approach. We revealed elevated GREM2 levels in severely obese subjects and validated this finding in a large-scale community population involving 10,327 subjects. Notably, serum GREM2 was positively associated with visceral fat volume, as quantified by 3D reconstruction methods. In mice, Grem2 was highly expressed in visceral fat and liver tissues, while surgical removal of visceral fat lowered circulating Grem2 levels. Visceral fat secreted more Grem2 in obese mice. Grem2-overexpressed mice exhibited a reduced browning ability of visceral fat, whereas Grem2 ablation enhanced the browning capacity and reduced visceral fat content. Mechanistically, Grem2 attenuated the browning program of visceral preadipocytes partially by antagonizing BMP4/7-SMAD1/5/8 signaling pathway. Further, genetic deletion of Bmpr2 in Pdgfrα+ preadipocytes abolished the antagonistic effect of Grem2. INTERPRETATION: These findings indicate that GREM2 might function as a circulating protein factor associated with human visceral adiposity, and Grem2 inhibits the browning capacity of visceral preadipocytes partially by BMP4/7-BMPR2 signaling pathway. FUNDING: The complete list of funders can be found in the Acknowledgement section.

Metal-hydrogen-pi-bonded organic frameworks.

We report the synthesis and characterization of a new series of permanently porous, three-dimensional metal-organic frameworks (MOFs), M-HAF-2 (M = Fe, Ga, or In), constructed from tetratopic, hydroxamate-based, chelating linkers. The structure of M-HAF-2 was determined by three-dimensional electron diffraction (3D ED), revealing a unique interpenetrated hcb-a net topology. This unusual topology is enabled by the presence of free hydroxamic acid groups, which lead to the formation of a diverse network of cooperative interactions comprising metal-hydroxamate coordination interactions at single metal nodes, staggered π-π interactions between linkers, and H-bonding interactions between metal-coordinated and free hydroxamate groups. Such extensive, multimodal interconnectivity is reminiscent of the complex, noncovalent interaction networks of proteins and endows M-HAF-2 frameworks with high thermal and chemical stability and allows them to readily undergo postsynthetic metal ion exchange (PSE) between trivalent metal ions. We demonstrate that M-HAF-2 can serve as versatile porous materials for ionic separations, aided by one-dimensional channels lined by continuously π-stacked aromatic groups and H-bonding hydroxamate functionalities. As an addition to the small group of hydroxamic acid-based MOFs, M-HAF-2 represents a structural merger between MOFs and hydrogen-bonded organic frameworks (HOFs) and illustrates the utility of non-canonical metal-coordinating functionalities in the discovery of new bonding and topological patterns in reticular materials.

Cyclic Trinuclear Copper(I) Complex Exhibiting Aggregation-Induced Emission: A Novel Fluorescent Probe for the Selective Detection of Gold(III) Ions.

Coordination complexes with aggregation-induced-emission (AIE) behavior has drawn much attention because of their promising applications. Conventionally, the AIE-active metal-organic complexes are prepared from an AIE-active organic ligand, and the construction of such coordination complexes from aggregation-caused-quenching (ACQ) ligands is still challenging. Herein, we have synthesized two new cyclic trinuclear complexes (CTCs), namely, 1 and 2, from copper(I) and silver(I) and a ACQ ligand [4-(3,5-dimethyl-1H-pyrazol-4-yl)benzaldehyde, HL]. (1) exhibited AIE behavior, and the emission intensity is enhanced ∼20 times when it aggregates, which can be attributed to its tight packing and multiple intermolecular hydrogen bonds that restrained the intramolecular rotation, as confirmed by single-crystal X-ray diffraction analysis. On the other hand, (2) displayed ACQ effects, and the emission intensity is decreased ∼5 times when it aggregates. This ACQ behavior of 2 is related to its loose packing and free rotation of the ligand in crystals, resulting in nonradiative decay and fluorescence quenching. Interestingly, the CTCs 1 and 2 both exhibited a good affinity to gold(III) ions, allowing selective detection and sensing of gold ions. More importantly, the 2 shows a good limit of detection (3.28 µmol/L) and an ultrafast responsive time (∼2 s). Our studies pave a new route to designing novel AIE-active coordination complexes and further exploring the functionality of CTCs.

Protein Assembly by Design.

Proteins are nature's primary building blocks for the construction of sophisticated molecular machines and dynamic materials, ranging from protein complexes such as photosystem II and nitrogenase that drive biogeochemical cycles to cytoskeletal assemblies and muscle fibers for motion. Such natural systems have inspired extensive efforts in the rational design of artificial protein assemblies in the last two decades. As molecular building blocks, proteins are highly complex, in terms of both their three-dimensional structures and chemical compositions. To enable control over the self-assembly of such complex molecules, scientists have devised many creative strategies by combining tools and principles of experimental and computational biophysics, supramolecular chemistry, inorganic chemistry, materials science, and polymer chemistry, among others. Owing to these innovative strategies, what started as a purely structure-building exercise two decades ago has, in short order, led to artificial protein assemblies with unprecedented structures and functions and protein-based materials with unusual properties. Our goal in this review is to give an overview of this exciting and highly interdisciplinary area of research, first outlining the design strategies and tools that have been devised for controlling protein self-assembly, then describing the diverse structures of artificial protein assemblies, and finally highlighting the emergent properties and functions of these assemblies.

Realization of Ethylene Production from Its Quaternary Mixture through Metal-Organic Framework Materials.

Ethylene production from oxidative coupling of methane is a sustainable and economically attractive alternative to that through traditional hydrocarbon cracking technology. However, efficient ethylene separation from the complex reaction mixture is a daunting challenge that hinders the practical adoption of this technology. Herein, we report the efficient adsorptive separation of the CH4/CO2/C2H4/C2H6 mixture using three representative metal-organic frameworks (MOFs) (UTSA-74, MOF-74, and HKUST-1) with diverse open metal sites. The efficient separation relies on tuning the selectivity through the convergence of characteristics including Lewis acidity of open metal sites, pore space, and cooperative binding behavior. The separation performance of these materials has been evaluated through single-component gas adsorption and dynamic breakthrough experiments. HKUST-1 provides the highest separation potential (4.1 mmol/g) thanks to its simultaneously high ideal adsorbed solution theory (IAST) selectivity and ethylene adsorption capacity, representing a benchmark material for such a challenging quaternary separation.

IRX3 Overexpression Enhances Ucp1 Expression In Vivo.

Objective: The Iroquois homeobox 3 (IRX3) gene was recently reported to be a functional downstream target of a common polymorphism in the FTO gene, which encodes an obesity-associated protein; however, the role of IRX3 in energy expenditure remains unclear. Studies have revealed that the overexpression of a dominant-negative form of IRX3 in the mouse hypothalamus and adipose tissue promoted energy expenditure by enhancing brown/browning activities. Meanwhile, we and others recently demonstrated that IRX3 knockdown impaired the browning program of primary preadipocytes in vitro. In this study, we aimed to further clarify the effects of overexpressing human IRX3 (hIRX3) on brown/beige adipose tissues in vivo. Methods: Brown/beige adipocyte-specific hIRX3-overexpressing mice were generated and the browning program of white adipose tissues was induced by both chronic cold stimulation and CL316,243 injection. Body weight, fat mass, lean mass, and energy expenditure were measured, while morphological changes and the expression of thermogenesis-related genes in adipose tissue were analyzed. Moreover, the browning capacity of primary preadipocytes derived from hIRX3-overexpressing mice was assessed. RNA sequencing was also employed to investigate the effect of hIRX3 on the expression of thermogenesis-related genes. Results: hIRX3 overexpression in embryonic brown/beige adipose tissues (Rosa26hIRX3 ;Ucp1-Cre) led to increased energy expenditure, decreased fat mass, and a lean body phenotype. After acute cold exposure or CL316,243 stimulation, brown/beige tissue hIRX3-overexpressing mice showed an increase in Ucp1 expression. Consistent with this, induced hIRX3 overexpression in adult mice (Rosa26hIRX3 ;Ucp1-CreERT2) also promoted a moderate increase in Ucp1 expression. Ex vitro experiments further revealed that hIRX3 overexpression induced by Ucp1-driven Cre recombinase activity upregulated brown/beige adipocytes Ucp1 expression and oxygen consumption rate (OCR). RNA sequencing analyses indicated that hIRX3 overexpression in brown adipocytes enhanced brown fat cell differentiation, glycolysis, and gluconeogenesis. Conclusion: Consistent with the in vitro findings, brown/beige adipocyte-specific overexpression of hIRX3 promoted Ucp1 expression and thermogenesis, while reducing fat mass.

Transferrin Receptor Functionally Marks Thermogenic Adipocytes.

BACKGROUND: Thermogenic adipocytes, including beige and brown adipocytes, are critical for thermogenesis and energy homeostasis. Identification of functional cell surface markers of thermogenic adipocytes is of significance for potential application in biological and clinical practices. METHODS: With a combination of RNA-sequencing of in vivo and in vitro models, we identified transferrin receptor (Tfr1), a receptor specialized for cellular iron uptake, as a previously unappreciated cell surface molecule for thermogenic adipocytes compared to white adipocytes. The alternation of Tfr1 levels under physiological and pathological stimuli was assessed, and the mitochondria functionality, browning capacity, and iron metabolism of mature adipocytes were examined with Tfr1 knockdown. RESULTS: Tfr1 was expressed predominantly in thermogenic adipocytes versus white adipocyte, and its expression levels were tightly correlated with the activation or inhibition status of thermogenic adipocytes under external stimuli. Besides, Tfr1 gene deficiency in thermogenic adipocytes led to reduced thermogenic gene programs and mitochondrial integrity. CONCLUSION: Tfr1 functionally marks thermogenic adipocytes and could serve as a potential thermogenic adipocyte surface marker.

Combination of Composite Autonomic Symptom Score 31 and Heart Rate Variability for Diagnosis of Cardiovascular Autonomic Neuropathy in People with Type 2 Diabetes.

OBJECTIVE: Cardiovascular autonomic neuropathy (CAN) is a common but severe problem of diabetes, which a timely diagnosis may have important clinical implications. This study was carried out to investigate the diagnostic performance of Composite Autonomic Symptom Score 31 (COMPASS 31) combined with heart rate variability (HRV) for cardiovascular autonomic neuropathy in type 2 diabetes. METHODS: A total of 103 hospitalized subjects with type 2 diabetes were recruited in the study. All cases received clinical data collection, laboratory examination, and related complication examinations. Cardiovascular autonomic function was assessed using CARTs, COMPASS 31, and HRV analyses. A score of at least 2 based on CARTs was defined as CAN. RESULTS: Of the 103 subjects with type 2 diabetes, 41.8% were diagnosed with confirmed CAN. Participants with CAN had considerably higher COMPASS 31 scores. The CAN group showed a significant decrease in all HRV indices. COMPASS 31 scores and HRV indices were closely correlated with CARTs (P < 0.05). Receiver operating characteristics (ROC) curve results showed that COMPASS 31 score identified CAN with an AUC value of 0.816, while the AUC values of HRV indices were 0.648 to 0.919, among which SDNN and LF had the best diagnostic value, with the AUC values of 0.919 and 0.865, respectively. When combining COMPASS 31 score with SDNN and LF, the AUC value increased to 0.958, with a sensitivity of 90.7% and a specificity of 86.7%. CONCLUSIONS: The combination of COMPASS 31 and HRV could improve the diagnostic performance of CAN in type 2 diabetes, which might be conducive to the diagnosis of CAN.

[Hydrochemical Characteristics and Possible Controls of the Surface Water in Ranwu Lake Basin].

To study the chemistry of surface water and potential control measures in the Ranwu Lake basin, 19 samples were collected from Ranwu Lake in 2019. Conventional hydrochemical techniques and statistical analysis methods (descriptive statistics, the Gibbs figure, ion ratio, Piper triangular diagrams) were applied to better understand the solute geochemistry and surface water hydrochemistry in the Ranwu Lake catchment. Surface water in the Ranwu catchment is slightly alkaline (pH of the samples ranged from 7.54 to 8.48 with an average value of 8.06). The concentrations of total dissolved solids (TDS) in the water range from 59.89 to 96.75 mg ·L-1 with an average of 79.98 mg ·L-1, the total dissolved solids of all samples are less than 100 mg ·L-1 and belong to fresh water. The TDS are dominated by Ca2+, Mg2+, HCO3-, and SO42- in the Ranwu Lake. The ion concentrations in the lake water samples are in the order of Ca2+ > Mg2+ > Na+ > K+. The concentrations of Na+and K+are very low. Ranging from 0.5 to 1.21 mg ·L-1, with an average value of 0.58 mg ·L-1, the equivalent concentration of Ca2+ accounts for 63.3% to 76.2% of total cations with an average value of 67.2%. The equivalent concentration of Mg2+ accounts for 23.4% to 36.2% of total cations with an average value of 31.4%. Ca2+ and Mg2+ account for 98.5% of total cations. The main anions were HCO3- and SO42-. The equivalent concentration of HCO3- accounts for 74.31% to 84.29% of total anions with an average value of 78.21%. The equivalent concentration of SO42- accounts for 9.59% to 19.37% of total anions with an average value of 15.34%. HCO3- and SO42- together account for 93.55% of total anions on average. All the water samples fall in the water-rock interaction field, which suggests that the weathering of rocks primarily controls the major ion chemistry of groundwater in this area. Solutes are mainly derived from carbonate weathering and silicate weathering. The role of cation exchange in the geochemical process of the lake and the influence of human activities on the lake are found to be weak.