Sex-Specific Appetite Regulation of Lipocalin-2 in High-Fat-Diet-Induced Obese Mice.

INTRODUCTION: Lipocalin 2 (Lcn2) is a key factor in appetite suppression. However, the effect of Lcn2 on appetite in terms of sex differences has not been thoroughly studied. METHODS: Young (3-month-old) whole-body Lcn2 knockout (Lcn2-/-) mice were fed a normal diet (ND) or high-fat diet (HFD) for 8 weeks to investigate obesity, food intake, serum metabolism, hepatic lipid metabolism, and regulation of gastrointestinal hormones. RESULTS: Lcn2 deficiency significantly increased the body weight and food intake of male mice when fed ND instead of HFD and females when fed HFD but not ND. Compared to wild-type (WT) male mice, the adiponectin level and phosphorylated form of adenosine 5'-monophosphate-activated protein kinase (AMPK) in the hypothalamus were both increased in ND-fed Lcn2-/- male mice but decreased in HFD-fed Lcn2-/- male mice. However, in female mice, adiponectin and its energy metabolism pathway were not altered. Instead, estradiol was found to be substantially higher in ND-fed Lcn2-/- female mice and substantially lower in HFD-fed Lcn2-/- female mice compared with WT female mice. Estradiol alteration also caused similar changes in ERα in the hypothalamus, leading to changes in the PI3K/AKT energy metabolism pathway. It suggested that the increased appetite caused by Lcn2 deficiency in male mice may be due to increased adiponectin expression and promotion of AMPK phosphorylation, while in female mice it may be related to the decrease of circulating estradiol and the inhibition of the hypothalamic ERα/PI3K/AKT energy metabolism pathway. CONCLUSION: Lcn2 plays in a highly sex-specific manner in the regulation of appetite in young mice.

Hydroxychloroquine Attenuates hERG Channel by Promoting the Membrane Channel Degradation: Computational Simulation and Experimental Evidence for QT-Interval Prolongation with Hydroxychloroquine Treatment.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to millions of confirmed cases and deaths worldwide and has no approved therapy. Currently, more than 700 drugs are tested in the COVID-19 clinical trials, and full evaluation of their cardiotoxicity risks is in high demand. METHODS: We mainly focused on hydroxychloroquine (HCQ), one of the most concerned drugs for COVID-19 therapy, and investigated the effects and underlying mechanisms of HCQ on hERG channel via molecular docking simulations. We further applied the HEK293 cell line stably expressing hERG-wild-type channel (hERG-HEK) and HEK293 cells transiently expressing hERG-p.Y652A or hERG-p.F656A mutants to validate our predictions. Western blot analysis was used to determine the hERG channel, and the whole-cell patch clamp was utilized to record hERG current (IhERG). RESULTS: HCQ reduced the mature hERG protein in a time- and concentration-dependent manner. Correspondingly, chronic and acute treatment of HCQ decreased the hERG current. Treatment with brefeldin A (BFA) and HCQ combination reduced hERG protein to a greater extent than BFA alone. Moreover, disruption of the typical hERG binding site (hERG-p.Y652A or hERG-p.F656A) rescued HCQ-mediated hERG protein and IhERG reduction. CONCLUSION: HCQ can reduce the mature hERG channel expression and IhERG via enhancing channel degradation. The QT prolongation effect of HCQ is mediated by typical hERG binding sites involving residues Tyr652 and Phe656.

Visualize the vibronic coupling in Auger final states in N2 molecule.

Vibronic coupling is a critical mechanism in chemical reactions. However, its quantitative evaluation is challenging due to mathematical complexity and programming difficulty, and its experimental proof is often elusive due to overlap among neighboring states. Here, after exciting a vibrational level (ν = 0, 1, 2) of the intermediate N 1s→πg* core-excited state in N2 molecules, we separate the resonant Auger decay channels that lead to the lowest dissociation limit in the two-dimensional energy correlation maps. From three kinetic energy release spectra of these channels at different vibrational quantum numbers, we give the first experimental proof of the vibronic coupling between two resonant Auger final states 12Πg and 22Πg.

Re-Imagining Drug Discovery using Mass Spectrometry.

It is argued that each of the three key steps in drug discovery, (i) reaction screening to find successful routes to desired drug candidates, (ii) scale up of the synthesis to produce amounts adequate for testing, and (iii) bioactivity assessment of the candidate compounds, can all be performed using mass spectrometry (MS) in a sequential fashion. The particular ionization method of choice, desorption electrospray ionization (DESI), is both an analytical technique and a procedure for small-scale synthesis. It is also highly compatible with automation, providing for high throughput in both synthesis and analysis. Moreover, because accelerated reactions take place in the secondary DESI microdroplets generated from individual reaction mixtures, this allows either online analysis by MS or collection of the synthetic products by droplet deposition. DESI also has the unique advantage, amongst spray-based MS ionization methods, that complex buffered biological solutions can be analyzed directly, without concern for capillary blockage. Here, all these capabilities are illustrated, the unique chemistry at droplet interfaces is presented, and the possible future implementation of DESI-MS based drug discovery is discussed.

Sound of Daily Living Identification Based on Hierarchical Situation Audition.

One of the key objectives in developing IoT applications is to automatically detect and identify human activities of daily living (ADLs). Mobile phone users are becoming more accepting of sharing data captured by various built-in sensors. Sounds detected by smartphones are processed in this work. We present a hierarchical identification system to recognize ADLs by detecting and identifying certain sounds taking place in a complex audio situation (AS). Three major categories of sound are discriminated in terms of signal duration. These are persistent background noise (PBN), non-impulsive long sounds (NILS), and impulsive sound (IS). We first analyze audio signals in a situation-aware manner and then map the sounds of daily living (SDLs) to ADLs. A new hierarchical audible event (AE) recognition approach is proposed that classifies atomic audible actions (AAs), then computes pre-classified portions of atomic AAs energy in one AE session, and finally marks the maximum-likelihood ADL label as the outcome. Our experiments demonstrate that the proposed hierarchical methodology is effective in recognizing SDLs and, thus, also in detecting ADLs with a remarkable performance for other known baseline systems.

High-Throughput Diversification of Complex Bioactive Molecules by Accelerated Synthesis in Microdroplets.

Late-stage diversification of drug molecules is an important strategy in drug discovery that can be facilitated by reaction screening using high-throughput experimentation. Here we present a rapid method for functionalizing bioactive molecules based on accelerated reactions in microdroplets. Reaction mixtures are nebulized at throughputs better than 1 reaction/second and the accelerated reactions occurring in the microdroplets are followed by desorption electrospray ionization mass spectrometry (DESI-MS). Because the accelerated reactions occur on the millisecond timescale, they allow an overall screening throughput of 1 Hz working at the low nanogram scale. Using this approach, an opioid agonist (PZM21) and an antagonist (naloxone) were diversified using three reactions important in medicinal chemistry: sulfur fluoride exchange (SuFEx) click reactions, imine formation reactions, and ene-type click reactions. Some 269 functionalized analogs of naloxone and PZM21 were generated and characterized by tandem mass spectrometry (MS/MS) after screening over 500 reactions.

Use of chimeric antigen receptor NK-92 cells to target mesothelin in ovarian cancer.

Mesothelin (MSLN) has been reported to be overexpressed in ovarian cancer and may be an ideal target for immunotherapy. Recent studies have suggested that natural killer (NK) cells may be better chimeric antigen receptor (CAR) drivers because of their favorable innate characteristics, such as directly recognizing and killing tumor cells, resulting in a graft-versus-tumor effect but irresponsible for graft-versus-host disease (GVHD). The therapeutic effects of CAR-engineered NK cells targeting MSLN in ovarian cancer have not been evaluated. In this study, MSLN- and CD19-targeted CAR NK-92 (MSLN- and CD19-CAR NK) cells were constructed. Both MSLN- and CD19-CAR molecules were highly expressed on the surface of NK-92 cells following lentiviral gene transduction. MSLN-CAR NK cells specifically killed MSLN-positive ovarian cancer cells (OVCAR-3 and SK-OV-3), rather than MSLN-negative cells (SK-HEP-1), in vitro. Moreover, compared with parental NK-92 cells and CD19-CAR NK cells, stronger cytokine secretion was detected in MSLN-CAR NK cells cocultured with OVCAR-3 and SK-OV-3. Furthermore, MSLN-CAR NK cells effectively eliminated ovarian cancer cells in both subcutaneous and intraperitoneal tumor models; these cells also significantly prolonged the survival of intraperitoneally tumor-bearing mice. These results demonstrate that MSLN-CAR NK cells have robust specific antitumor activity, both in vitro and in vivo, suggesting that mesothelin could be a potential target for CAR NK cells and could be applied in the treatment of ovarian cancer.

Sensor Fusion for Recognition of Activities of Daily Living.

Activity of daily living (ADL) is a significant predictor of the independence and functional capabilities of an individual. Measurements of ADLs help to indicate one's health status and capabilities of quality living. Recently, the most common ways to capture ADL data are far from automation, including a costly 24/7 observation by a designated caregiver, self-reporting by the user laboriously, or filling out a written ADL survey. Fortunately, ubiquitous sensors exist in our surroundings and on electronic devices in the Internet of Things (IoT) era. We proposed the ADL Recognition System that utilizes the sensor data from a single point of contact, such as smartphones, and conducts time-series sensor fusion processing. Raw data is collected from the ADL Recorder App constantly running on a user's smartphone with multiple embedded sensors, including the microphone, Wi-Fi scan module, heading orientation of the device, light proximity, step detector, accelerometer, gyroscope, magnetometer, etc. Key technologies in this research cover audio processing, Wi-Fi indoor positioning, proximity sensing localization, and time-series sensor data fusion. By merging the information of multiple sensors, with a time-series error correction technique, the ADL Recognition System is able to accurately profile a person's ADLs and discover his life patterns. This paper is particularly concerned with the care for the older adults who live independently.

High-throughput label-free opioid receptor binding assays using an automated desorption electrospray ionization mass spectrometry platform.

The current opioid epidemic has incentivized the discovery of new non-addictive analgesics, a process that requires the screening of opioid receptor binding, traditionally performed using radiometric assays. Here we describe a label-free alternative based on high-throughput (1 Hz) ambient mass spectrometry for screening the receptor binding of new opioid analogues.

Perioperative intravenous infusion of dexmedetomidine for alleviating postpartum depression after cesarean section: A meta-analysis and systematic review.

The efficacy of perioperative dexmedetomidine (DEX) infusion as a precaution against postpartum depression (PPD) in women undergoing cesarean section has not been substantiated systematically. A literature search for RCTs on DEX against PPD was retrieved in the following databases from inception to January 3, 2024: PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Wanfang, CBM, VIP, etc. A total of 13 RCTs with 1711 participants were included. Meta-analysis was performed by RevMan5.3 and Stata16 using a random-effects model. EPDS scores were significantly decreased in the DEX group within one week or over one week postpartum compared to the control group (SMD = -1.25, 95 %CI: -1.73 to -0.77; SMD = -1.08, 95 %CI: -1.43 to -0.73). The prevalence of PPD was significantly inferior to the control at both time points (RR = 0.36, 95 %CI: 0.24 to 0.54; RR = 0.39, 95 %CI: 0.26 to 0.57). Univariate meta-regression suggested that age influenced the heterogeneity of the EPDS scores (P = 0.039), and DEX infusion dose was a potential moderator (P = 0.074). The subgroup analysis results of PPD scores at both time points were consistent, showing that: ① Mothers younger than 30 years old had better sensitivity to DEX for treating PPD. ② The anti-PPD efficacy of continuous infusion of DEX by PCIA was superior to both single infusion and combined infusion. ③ DEX showed a better anti-PPD effect when the total infusion dose was ≤ 2 µg/kg. Moreover, DEX improved analgesia and sleep quality, provided appropriate sedation, and reduced the incidence of nausea, vomiting, and chills. The current evidence confirmed the prophylaxis and superiority of DEX for PPD. More high-quality, large-scale RCTs are required for verifying the reliability and formulating administration methods.

Effect of Dexmedetomidine on Postpartum Depression in Women With Prenatal Depression: A Randomized Clinical Trial.

Importance: Postpartum depression (PPD) is emerging as a major public health problem worldwide. Although the particular period and context in which PPD occurs provides an opportunity for preventive interventions, there is still a lack of pharmacologic prevention strategies for PPD. Objective: To assess the efficacy and safety of dexmedetomidine for prevention of PPD among women with prenatal depression undergoing cesarean delivery. Design, Setting, and Participants: This randomized clinical trial enrolled 338 women who screened positive for prenatal depression at 2 hospitals in Hunan, China from March 28, 2022, to April 16, 2023. Women with an Edinburgh Postnatal Depression Scale score of more than 9 who were 18 years of age or older and were scheduled for elective cesarean delivery were eligible. Interventions: Eligible participants were randomly assigned in a 1:1 ratio to either the dexmedetomidine group or the control group via centrally computer-generated group randomization. Dexmedetomidine, 0.5 µg/kg and 0.9% saline were intravenously infused for 10 minutes after delivery in the dexmedetomidine and control groups, respectively. After infusion, sufentanil or dexmedetomidine plus sufentanil was administered via patient-controlled intravenous analgesia for 48 hours in the control group and dexmedetomidine group, respectively. Main Outcomes and Measures: The primary outcome was positive PPD screening results at 7 and 42 days post partum, defined as a postpartum Edinburgh Postnatal Depression Scale score of more than 9. Analysis was on an intention-to-treat basis. Results: All 338 participants were female, with a mean (SD) age of 31.5 (4.1) years. Positive PPD screening incidence at 7 and 42 days post partum in the dexmedetomidine group vs the control group was significantly decreased (day 7, 21 of 167 [12.6%] vs 53 of 165 [32.1%]; risk ratio, 0.39 [95% CI, 0.25-0.62]; P < .001; day 42, 19 of 167 [11.4%] vs 50 of 165 [30.3%]; risk ratio, 0.38 [95% CI, 0.23-0.61]; P < .001). The dexmedetomidine group showed no significant difference in adverse events vs the control group (46 of 169 [27.2%] vs 33 of 169 [19.5%]; P = .10), but the incidence of hypotension increased (31 of 169 [18.3%] vs 16 of 169 [9.5%]; risk ratio, 2.15 [95% CI, 1.13-4.10]; P = .02). Conclusions and Relevance: Dexmedetomidine administration in the early postpartum period significantly reduced the incidence of a positive PPD screening and maintained a favorable safety profile. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200057213.

Iron Chelator Deferoxamine Alleviates Progression of Diabetic Nephropathy by Relieving Inflammation and Fibrosis in Rats.

Diabetic nephropathy (DN) is one of the most devastating diabetic microvascular complications. It has previously been observed that iron metabolism levels are abnormal in diabetic patients. However, the mechanism by which iron metabolism levels affect DN is poorly understood. This study was designed to evaluate the role of iron-chelator deferoxamine (DFO) in the improvement of DN. Here, we established a DN rat model induced by diets high in carbohydrates and fat and streptozotocin (STZ) injection. Our data demonstrated that DFO treatment for three weeks greatly attenuated renal dysfunction as evidenced by decreased levels of urinary albumin, blood urea nitrogen, and serum creatinine, which were elevated in DN rats. Histopathological observations showed that DFO treatment improved the renal structures of DN rats and preserved podocyte integrity by preventing the decrease of transcripts of nephrin and podocin. In addition, DFO treatment reduced the overexpression of fibronectin 1, collagen I, IL-1ß, NF-κB, and MCP-1 in DN rats, as well as inflammatory cell infiltrates and collagenous fibrosis. Taken together, our findings unveiled that iron chelation via DFO injection had a protective impact on DN by alleviating inflammation and fibrosis, and that it could be a potential therapeutic strategy for DN.

The burden of cardiovascular diseases attributable to metabolic risk factors and its change from 1990 to 2019: a systematic analysis and prediction.

Background: Metabolic disorders are the most important risk factors for cardiovascular diseases (CVDs). The purpose of this study was to systematically analyze and summarize the most recent data by age, sex, region, and time, and to forecast the future burden of diseases. Methods: Data on the burden of CVDs associated with metabolic risk factors were obtained from the Global Burden of Disease (GBD) Study 2019; and then the burden of disease was assessed using the numbers and age-standardized rates (ASR) of deaths, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) and analyzed for temporal changes, differences in age, region, sex, and socioeconomic aspects; finally, the burden of disease was predicted using an autoregressive integrated moving average (ARIMA) model. Results: From 1990 to 2019, the numbers of deaths, DALYs, YLDs, and YLLs attributed to metabolic risk factors increased by 59.3%, 51.0%, 104.6%, and 47.8%, respectively. The ASR decreased significantly. The burden of metabolic risk factor-associated CVDs was closely related to socioeconomic position and there were major geographical variations; additionally, men had a significantly greater disease burden than women, and the peak shifted later based on the age group. We predicted that the numbers of deaths and DALYs would reach 16.5 million and 324.8 million, respectively, by 2029. Conclusions: The global burden of CVDs associated with metabolic risk factors is considerable and still rising, and more effort is needed to intervene in metabolic disorders.

Correlations between GRIN2B and GRIN3A gene polymorphisms and postpartum depressive symptoms in Chinese parturients undergoing cesarean section: A prospective cohort study.

OBJECTIVE: To investigate the association of postpartum depressive symptoms (PDS) and self-harm ideation with n-methyl-d-aspartate (NMDA) receptor GRIN2B and GRIN3A gene polymorphisms and other risk factors in women undergoing cesarean section. METHODS: A total of 362 parturients undergoing cesarean section under lumbar anesthesia were selected and their postpartum depression level was assessed by the Edinburgh Postpartum Depression Scale (EPDS) at 42 days postpartum, with an EPDS score of 9/10 as the cut-off value. Three GRIN2B SNP loci (rs1805476, rs3026174, rs4522263) and five GRIN3A SNP loci (rs1983812, rs2050639, rs2050641, rs3739722, rs10989563) were selected for genotype detection. The role of each SNP, linkage disequilibrium and haplotypes in the development of postpartum depression was analyzed. Logistic regression analysis was performed for related risk factors. RESULTS: PDS incidence was 16.85%, and self-harm ideation incidence was 13.54%. Univariate analysis showed that GRIN2B rs1805476, rs3026174 and rs4522263 gene polymorphisms were associated with PDS (p < 0.05), with GRIN2B rs4522263 gene also associated with maternal self-harm ideation. GRIN3A rs1983812, rs2050639, rest rs2050641, rs3739722 and rs10989563 alleles were not associated with PDS. Logistic regression analysis indicated that high pregnancy stress, as well as rs1805476 and rs4522263 alleles were PDS risk factors following cesarean delivery. GRIN2B (TTG p = 0.002) and GRIN3A (TGTTC p = 0.002) haplotypes were associated with the lower PDS incidence and higher PDS incidence respectively. CONCLUSION: GRIN2B rs1805476 GG genotype, rs4522263 CC genotype and high stress during pregnancy were risk factors for PDS, whilst a significantly higher incidence of self-harm ideation was evident in parturients carrying GRIN2B rs4522263 CC genotype.

Prognosis and subtype analysis of left ventricular noncompaction in adults: A retrospective multicenter study.

BACKGROUND: Left ventricular noncompaction (LVNC) is a heterogeneous myocardial disorder with an uncertain prognosis. There was a lack of studies on LVNC subtypes at present. This study sought to identify the prognosis of the overall population of LVNC and to describe the distribution of different subtypes and compare their prognosis. HYPOTHESIS: Patients with different subtypes of LVNC may have different prognoses. METHODS: Patients who fulfilled the Jenni criteria and/or Petersen criteria were included. Major adverse cardiovascular events (MACE) were defined as a combination of heart failure (HF) hospitalization and all-cause mortality. RESULTS: A total of 200 patients from four hospitals were included. The mean age at diagnosis was 48.2 years, and 61.5% of the patients were male. Left ventricular ejection fraction (LVEF) < 50% was present in 54% of the patients. Over a mean retrospective time period of 22.2 months, 47 (23.5%) patients experienced MACE. Age (hazard ratio [HR] 1.03; 95% confidence interval [CI] 1.01-1.06; p = .004), LVEF < 50% (HR 2.32; 95% CI 1.09-4.91; p = .028) and ventricular tachycardia/ventricular fibrillation (HR 2.17; 95% CI 1.08-4.37; p = .03) were significantly associated with the risk of MACE. The most common subtype was dilated LVNC (51.3%), followed by benign LVNC (21.3%) and LVNC with arrhythmias (10.5%). Patients with dilated LVNC had significantly increased cumulative incidence of MACE, HF hospitalization, and all-cause mortality (p < .05). CONCLUSIONS: Age, LVEF < 50%, and ventricular tachycardia/ventricular fibrillation were independent risk factors for prognosis of LVNC. The most common subtype was dilated LVNC, which had a worse prognosis.

An optimization for postpartum depression risk assessment and preventive intervention strategy based machine learning approaches.

BACKGROUND: Postpartum depression (PPD) is one of the most common psychiatric disorders for women after delivery. The establishment of an effective PPD prediction model helps to distinguish high-risk groups, and verifying whether such high-risk groups can benefit from drug intervention is very important for clinical guidance. METHODS: We collected data of parturients that underwent a cesarean delivery. The Control group was divided into a training cohort and a testing cohort. Six different ML models were constructed and we compared their prediction performance in the testing cohort. For model interpretation, we introduced SHapley Additive exPlanations (SHAP). Then, training cohort, ketamine group and dexmedetomidine (DEX) group were classified as high or low risk for PPD by the model. A 1:1 propensity score matching (PSM) was performed to compare the incidence of PPD between two groups in different risk cohorts. RESULTS: Extreme gradient enhancement (XGB) had the best recognition effect, with an area under the receiver operating characteristic curve (AUROC) of 0.789 (95 % CI 0.742-0.836) in the training cohort and 0.744 (95 % CI 0.655-0.823) in the testing cohort, respectively. A threshold of 21.5 % PPD risk probability was determined. After PSM, the results showed that the incidence of PPD in the two intervention groups was significantly different from the control group in the high-risk cohort (P < 0.001) but not in the low-risk cohort (P > 0.001). CONCLUSION: Our study demonstrated that the XGB algorithm provided a more accurate in prediction of PPD risk, and it was beneficial to receive early intervention for the high-risk groups distinguished by the model.

Predicting efficacy of sub-anesthetic ketamine/esketamine i.v. dose during course of cesarean section for PPD prevention, utilizing traditional logistic regression and machine learning models.

OBJECTIVE: Increasing researches supported that intravenous ketamine/esketamine during the perioperative period of cesarean section could prevent postpartum depression(PPD). With the effective rate ranging from 87.2 % to 95.5 % in PPD, ketamine/esketamine's responsiveness was individualized. To optimize ketamine dose/form based on puerpera prenatal characteristics, reducing adverse events and improving the total efficacy rate, prediction models were developed to predict ketamine/esketamine's efficacy. METHOD: Based on two randomized controlled trials, 12 prenatal features of 507 women administered the ketamine/esketamine intervention were collected. Traditional logistics regression, SVM, random forest, KNN and XGBoost prediction models were established with prenatal features and dosage regimen as predictors. RESULTS: According to the logistic regression model (ain = 0.10, aout = 0.15, area under the receiver operating characteristic curve, AUC = 0.728), prenatal Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10, thoughts of self-injury and bad mood during pregnancy were associated with poorer ketamine efficacy in PPD prevention, whilst a high dose of esketamine (0.25 mg/kg loading dose+2 mg/kg PCIA) was the most effective dosage regimen and esketamine was more recommended rather than ketamine in PPD. The AUCvalidation set of KNN and XGBoost model were 0.815 and 0.651, respectively. CONCLUSION: Logistic regression and machine learning algorithm, especially the KNN model, could predict the effectiveness of ketamine/esketamine iv. during the course of cesarean section for PPD prevention. An individualized preventative strategy could be developed after entering puerpera clinical features into the model, possessing great clinical practice value in reducing PPD incidence.

Giant cystic parathyroid adenoma: two case reports and a literature review.

An uncommon cause of primary hyperparathyroidism is a cystic parathyroid adenoma. This paper describes two patients with hypercalcemia and right knee disease. Their serum calcium concentration was high, phosphorus concentration was low, and parathyroid hormone (PTH) concentration was high. Ultrasound and computed tomography scans of the neck indicated a cystic mass near the thyroid. Parathyroid scintigraphy showed no focal uptake in one patient and low tracer concentration in the cystic mass in the other patient. Following resection of the cystic masses, both were pathologically confirmed to be a cystic parathyroid adenoma with predominantly cystic degeneration. The calcium and PTH concentrations gradually decreased to the reference range. Both patients were stable at their last follow-up. The diagnosis of a functional cystic parathyroid adenoma is highly challenging because of the different clinical manifestations and negative result on parathyroid tracer scintigraphy. For patients with high serum calcium and PTH concentrations and a cystic mass in the neck, resection of the mass and subsequent postoperative pathological diagnosis is necessary even if the clinical diagnosis of a parathyroid adenoma cannot be confirmed preoperatively. Decreases in the PTH and serum calcium concentrations indicate successful resection of a functional parathyroid adenoma.

Dietary iron modulates hepatic glucose homeostasis via regulating gluconeogenesis.

Iron exerts significant influences on glucose metabolism. However, the regulatory mechanisms underlying disordered glucose response remains largely unclear. The aim of this study was to examine the impact of dietary iron on hepatic gluconeogenesis in mice and in rat liver-derived cells. High iron models of C57BL/6J mice were fed with 1.25 g Fe/kg diets for 9 weeks, and high-iron BRL-3A cell models were treated with 250 µmol/L FeSO4 for 12 h and 24 h. Our data showed that higher iron intake resulted in higher hepatic iron without iron toxicity, and reduced body weight gain with no difference of food intakes. High dietary iron significantly increased 61% of hepatic glycogen deposition, but exhibited impairment in glucose responses in mice. Moreover, high dietary iron suppressed hepatic gluconeogenesis by repressing the expression of key gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Meanwhile, mice fed with higher iron diets exhibited both decreased AMP-activated protein kinase (AMPK) activity and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) protein levels. Furthermore, in BRL-3A cells, iron treatment increased cellular glucose uptake, and altered gluconeogenesis rhythmically by regulating the activation of AMPK and expression of PGC-1α successively. This study demonstrated that dietary high iron was able to increase hepatic glycogen deposition by enhancement of glucose uptake, and suppress hepatic gluconeogenesis by regulation of AMPK and PGC-1α.

Increasing connections among temporal invariability, resistance and resilience of alpine grasslands on the Tibetan Plateau.

Ecological stability contains multiple components, such as temporal invariability, resistance and resilience. Understanding the response of stability components to perturbations is beneficial for optimizing the management of biodiversity and ecosystem functioning. Although previous studies have investigated the effects of multiple perturbations on each stability component, few studies simultaneously measure the multiple stability components and their relationships. Alpine grasslands on the Tibetan Plateau are exposed to co-occurring perturbations, including climate change and human activities. Here, we quantified three stability components (temporal invariability, resistance, and resilience) of alpine grasslands on the Tibetan Plateau during periods of high (2000-2008) and low (2009-2017) human activity intensity, respectively. We focused on the effects of climate variables (temperature, precipitation, radiation) and human activities (grazing intensity) on covariation among stability components. The results show that (1) for periods of high and low human activity, temporal invariability was positively correlated with resistance and resilience, while resistance was independent of resilience; (2) the dimensionality of alpine grasslands decreased by almost 10%, from 0.61 in the first period to 0.55 in the second period, suggesting the increasing connections among temporal invariability, resistance and resilience of alpine grasslands; and (3) temperature but not grazing intensity dominated the changes in the dimensionality of stability. These findings improve our understanding of multi-dimensional stability and highlight the importance of climate variability on alpine grassland stability on the Tibetan Plateau.