Development and Validation of a Diagnostic Model for Identifying Clear Cell Renal Cell Carcinoma in Small Renal Masses Based on CT Radiological Features: A Multicenter Study.

RATIONALE AND OBJECTIVES: This study aimed to develop a diagnostic model based on clinical and CT features for identifying clear cell renal cell carcinoma (ccRCC) in small renal masses (SRMs). MATERIAL AND METHODS: This retrospective multi-centre study enroled patients with pathologically confirmed SRMs. Data from three centres were used as training set (n = 229), with data from one centre serving as an independent test set (n = 81). Univariate and multivariate logistic regression analyses were utilised to screen independent risk factors for ccRCC and build the classification and regression tree (CART) diagnostic model. The area under the curve (AUC) was used to evaluate the performance of the model. To demonstrate the clinical utility of the model, three radiologists were asked to diagnose the SRMs in the test set based on professional experience and re-evaluated with the aid of the CART model. RESULTS: There were 310 SRMs in 309 patients and 71% (220/310) were ccRCC. In the testing cohort, the AUC of the CART model was 0.90 (95% CI: 0.81, 0.97). For the radiologists' assessment, the AUC of the three radiologists based on the clinical experience were 0.78 (95% CI:0.66,0.89), 0.65 (95% CI:0.53,0.76), and 0.68 (95% CI:0.57,0.79). With the CART model support, the AUC of the three radiologists were 0.93 (95% CI:0.86,0.97), 0.87 (95% CI:0.78,0.95) and 0.87 (95% CI:0.78,0.95). Interobserver agreement was improved with the CART model aids (0.323 vs 0.654, P < 0.001). CONCLUSION: The CART model can identify ccRCC with better diagnostic efficacy than that of experienced radiologists and improve diagnostic performance, potentially reducing the number of unnecessary biopsies.

Development and validation of a nomogram to predict leptomeningeal metastases in lung adenocarcinoma: Cervical lymph node metastasis is an important association factor.

BACKGROUND: The goal of this study was to create a nomogram using routine parameters to predict leptomeningeal metastases (LMs) in advanced lung adenocarcinoma (LAC) patients to prevent needless exams or lumbar punctures and to assist in accurately diagnosing LMs. METHODS: Two hundred and seventy-three patients with LMs and brain metastases were retrospectively reviewed and divided into derivation (n = 191) and validation (n = 82) cohorts using a 3:7 random allocation. All LAC patients with LMs had positive cerebrospinal fluid cytology results and brain metastases confirmed by magnetic resonance imaging. Binary logistic regression with backward stepwise selection was used to identify significant characteristics. A predictive nomogram based on the logistic model was assessed through receiver operating characteristic curves. The validation cohort and Hosmer-Lemeshow test were used for internal validation of the nomogram. RESULTS: Five clinicopathological parameters, namely, gene mutations, surgery at the primary lung cancer site, clinical symptoms of the head, N stage, and therapeutic strategy, were used as predictors of LMs. The area under the curve was 0.946 (95% CI 0.912-0.979) for the training cohort and 0.861 (95% CI 0.761-0.961) for the internal validation cohort. There was no significant difference in performance between the two cohorts (p = 0.116). In the internal validation, calibration plots revealed that the nomogram predictions were well suited to the actual outcomes. CONCLUSIONS: We created a user-friendly nomogram to predict LMs in advanced lung cancer patients, which could help guide treatment decisions and reduce unnecessary lumbar punctures.

Global, Regional, and National Change Patterns in the Incidence of Low Back Pain From 1990 to 2019 and Its Predicted Level in the Next Decade.

Objectives: To analyze and describe the spatiotemporal trends of Low back pain (LBP) burdens from 1990 to 2019 and anticipate the following decade's incidence. Methods: Using data from the Global Burden of Disease (GBD) 2019 Study, we described net drifts, local drifts, age effects, and period cohort effects in incidence and forecasted incidence rates and cases by sex from 2020 to 2029 using the Nordpred R package. Results: LBP remained the leading cause of the musculoskeletal disease burden globally and across all socio-demographic index (SDI) regions. China is the top country. For recent periods, high-SDI countries faced unfavorable or worsening risks. The relative risk of incidence showed improving trends over time and in successively younger birth cohorts amongst low-middle-, middle- and high-middle-SDI countries. Additionally, the age-standardized incidence rates (ASIR) of LBP in both sexes globally showed a decreasing trend, but the incident cases would increase from 223 to 253 million overall in the next decade. Conclusion: As the population ages, incident cases will rise but ASIR will fall. To minimise LBP, public awareness and disease prevention and control are needed.

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

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

A novel electrochemical biosensor for B-type natriuretic peptide detection based on CRISPR/Cas13a and chain substitution reaction.

B-type natriuretic peptide (BNP) is a biomarker for heart failure, a serious and prevalent disease that requires rapid and accurate diagnosis. In this study, we developed a novel electrochemical biosensor for BNP detection based on CRISPR/Cas13a and chain substitution reaction. The biosensor consists of a DNA aptamer that specifically binds to BNP, a T7 RNA polymerase that amplifies the signal, a CRISPR/Cas13a system that cleaves the target RNA, and a two-dimensional DNA nanoprobe that generates an electrochemical signal. The biosensor exhibits high sensitivity, specificity, and stability, with a detection limit of 0.74 aM. The biosensor can also detect BNP in human serum samples with negligible interference, demonstrating its potential for clinical and point-of-care applications. This study presents a novel strategy for integrating CRISPR/Cas13a and chain substitution reaction into biosensor design, offering a versatile and effective platform for biomolecule detection.

Estrogen signaling in the dorsal raphe regulates binge-like drinking in mice.

Estrogens promote binge alcohol drinking and contribute to sex differences in alcohol use disorder. However, the mechanisms are largely unknown. This study aims to test if estrogens act on 5-hydroxytryptamine neurons in the dorsal raphe nucleus (5-HTDRN) to promote binge drinking. We found that female mice drank more alcohol than male mice in chronic drinking in the dark (DID) tests. This sex difference was associated with distinct alterations in mRNA expression of estrogen receptor α (ERα) and 5-HT-related genes in the DRN, suggesting a potential role of estrogen/ERs/5-HT signaling. In supporting this view, 5-HTDRN neurons from naïve male mice had lower baseline firing activity but higher sensitivity to alcohol-induced excitation compared to 5-HTDRN neurons from naïve female mice. Notably, this higher sensitivity was blunted by 17ß-estradiol treatment in males, indicating an estrogen-dependent mechanism. We further showed that both ERα and ERß are expressed in 5-HTDRN neurons, whereas ERα agonist depolarizes and ERß agonist hyperpolarizes 5-HTDRN neurons. Notably, both treatments blocked the stimulatory effects of alcohol on 5-HTDRN neurons in males, even though they have antagonistic effects on the activity dynamics. These results suggest that ERs' inhibitory effects on ethanol-induced burst firing of 5-HTDRN neurons may contribute to higher levels of binge drinking in females. Consistently, chemogenetic activation of ERα- or ERß-expressing neurons in the DRN reduced binge alcohol drinking. These results support a model in which estrogens act on ERα/ß to prevent alcohol-induced activation of 5-HTDRN neurons, which in return leads to higher binge alcohol drinking.

BGF-Net: Boundary guided filter network for medical image segmentation.

How to fuse low-level and high-level features effectively is crucial to improving the accuracy of medical image segmentation. Most CNN-based segmentation models on this topic usually adopt attention mechanisms to achieve the fusion of different level features, but they have not effectively utilized the guided information of high-level features, which is often highly beneficial to improve the performance of the segmentation model, to guide the extraction of low-level features. To address this problem, we design multiple guided modules and develop a boundary-guided filter network (BGF-Net) to obtain more accurate medical image segmentation. To the best of our knowledge, this is the first time that boundary guided information is introduced into the medical image segmentation task. Specifically, we first propose a simple yet effective channel boundary guided module to make the segmentation model pay more attention to the relevant channel weights. We further design a novel spatial boundary guided module to complement the channel boundary guided module and aware of the most important spatial positions. Finally, we propose a boundary guided filter to preserve the structural information from the previous feature map and guide the model to learn more important feature information. Moreover, we conduct extensive experiments on skin lesion, polyp, and gland segmentation datasets including ISIC 2016, CVC-EndoSceneStil and GlaS to test the proposed BGF-Net. The experimental results demonstrate that BGF-Net performs better than other state-of-the-art methods.

Retinal vessel segmentation based on multi-scale feature and style transfer.

Retinal vessel segmentation is very important for diagnosing and treating certain eye diseases. Recently, many deep learning-based retinal vessel segmentation methods have been proposed; however, there are still many shortcomings (e.g., they cannot obtain satisfactory results when dealing with cross-domain data or segmenting small blood vessels). To alleviate these problems and avoid overly complex models, we propose a novel network based on a multi-scale feature and style transfer (MSFST-NET) for retinal vessel segmentation. Specifically, we first construct a lightweight segmentation module named MSF-Net, which introduces the selective kernel (SK) module to increase the multi-scale feature extraction ability of the model to achieve improved small blood vessel segmentation. Then, to alleviate the problem of model performance degradation when segmenting cross-domain datasets, we propose a style transfer module and a pseudo-label learning strategy. The style transfer module is used to reduce the style difference between the source domain image and the target domain image to improve the segmentation performance for the target domain image. The pseudo-label learning strategy is designed to be combined with the style transfer module to further boost the generalization ability of the model. Moreover, we trained and tested our proposed MSFST-NET in experiments on the DRIVE and CHASE_DB1 datasets. The experimental results demonstrate that MSFST-NET can effectively improve the generalization ability of the model on cross-domain datasets and achieve improved retinal vessel segmentation results than other state-of-the-art methods.

Zhuifeng Tougu capsules in the treatment of knee osteoarthritis (cold dampness obstruction syndrome): a randomized, double blind, multicenter clinical study.

BACKGROUND: In Traditional Chinese Medicine (TCM) theory, cold dampness obstruction is one of the common syndromes of osteoarthritis. Therefore, in clinical practice, the main treatment methods are to dispel wind, remove dampness, and dissipate cold, used to treat knee osteoarthritis (KOA). This report describes a mulitercenter clinical study to assess Zhuifeng Tougu Capsule's efficacy and safety in the treatment of patients who are cold dampness obstruction syndrome in KOA, and to provide evidence-based medical for the rational use of Zhuifeng Tougu Capsules in clinical practice. METHODS: This randomized, parallel group controlled, double-blind, double dummy trial will include a total of 215 KOA patients who meet the study criteria. 215 patients underwent 1:1 randomisation, with 107 cases assigned the experimental group (Zhuifeng Tougu Capsules + Glucosamine Sulfate Capsules Simulator) and 108 assigned the control group (Glucosamine Sulfate Capsules + Zhuifeng Tougu Capsules Simulator). After enrolment, patients received 12 weeks of treatment. The main efficacy measure is the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score. Visual analogue scale (VAS) pain score, Self-condition assessment VAS score, WOMAC KOA score, TCM syndrome score and TCM syndrome efficacy, ESR level, CRP level, suprapatellar bursa effusion depth, use of rescue drugs, and safety indicators are secondary efficacy indicators. RESULTS: Compared with before treatment, WOMAC pain score, VAS pain score, Self-condition assessment VAS score, WOMAC KOA score, and TCM syndrome score decreased significantly in both groups (P < 0.01). Also, the experimental group showed significant differences in the above indicators compared to control (P < 0.01). However, after treatment, no significant differences were showed in the ESR level, CRP level, and suprapatellar bursa effusion depth between the two groups (P > 0.05). No any serious adverse effects showed in the experimental group and control group. CONCLUSIONS: Zhuifeng Tougu Capsules can effectively improve knee joint function and significantly alleviate the pain of KOA. TRIAL REGISTRATION: Clinical trial registration was completed with the China Clinical Trial Registration Center for this research protocol (No. ChiCTR2000028750) on January 2, 2020.

The global magnitude and temporal trend of rheumatoid arthritis burden attributable to smoking from 1990 to 2019.

OBJECTIVES: The relationship between smoking and RA has been confirmed. Most nations have ratified the Framework Convention on Tobacco Control. However, there are considerable regional differences in how effectively tobacco control measures were implemented. This study was carried out to estimate the spatiotemporal trends of smoking-related RA burdens. METHODS: Data were available from the Global Burden of Disease Study 2019 and were analysed by age, sex, year and region. Joinpoint regression analysis was applied to the analysis of temporal trends in the RA burden resulting from smoking over 30 years. RESULTS: From 1990 to 2019, the number of global RA cases increased each year. The age-standardized prevalence, death and disability-adjusted life-year (DALY) rates also increased. However, there was a wave in the changing trend of the age-standardized death rate, with the lowest point in 2012 and the highest point in 1990. Smoking, in particular, was responsible for 11.9% of total RA deaths and 12.8% of total DALYs in 1990 but only 8.5% of total RA deaths and 9.6% of total DALYs in 2019. A greater burden from smoking exposure was borne by men, older adults and people living in high-middle and high sociodemographic index (SDI) countries and regions. Moreover, the UK demonstrated the highest reduction in age-standardized death and DALY rates over the three decades. CONCLUSION: There were reductions in the age-standardized burdens of RA caused by smoking worldwide. Nevertheless, this continues to be an issue in some areas, and efforts to reduce smoking should be made to lessen this growing burden.

Estrogen prevents age-dependent beige adipogenesis failure through NAMPT-controlled ER stress pathway.

Thermogenic beige adipocytes are recognized as potential therapeutic targets for combating metabolic diseases. However, the metabolic advantages they offer are compromised with aging. Here, we show that treating mice with estrogen (E2), a hormone that decreases with age, to mice can counteract the aging- related decline in beige adipocyte formation when subjected to cold, while concurrently enhancing energy expenditure and improving glucose tolerance. Mechanistically, we find that nicotinamide phosphoribosyltranferase (NAMPT) plays a pivotal role in facilitating the formation of E2-induced beige adipocytes, which subsequently suppresses the onset of age-related ER stress. Furthermore, we found that targeting NAMPT signaling, either genetically or pharmacologically, can restore the formation of beige adipocytes by increasing the number of perivascular adipocyte progenitor cells. Conversely, the absence of NAMPT signaling prevents this process. In conclusion, our findings shed light on the mechanisms governing the age-dependent impairment of beige adipocyte formation and underscore the E2-NAMPT controlled ER stress as a key regulator of this process. Highlights: Estrogen restores beige adipocyte failure along with improved energy metabolism in old mice.Estrogen enhances the thermogenic gene program by mitigating age-induced ER stress.Estrogen enhances the beige adipogenesis derived from SMA+ APCs.Inhibiting the NAMPT signaling pathway abolishes estrogen-promoted beige adipogenesis.

Si-Based Polarizer and 1-Bit Phase-Controlled Non-Polarizing Beam Splitter-Based Integrated Metasurface for Extended Shortwave Infrared.

Metasurfaces, composed of micro-nano-structured planar materials, offer highly tunable control over incident light and find significant applications in imaging, navigation, and sensing. However, highly efficient polarization devices are scarce for the extended shortwave infrared (ESWIR) range (1.7~2.5 µm). This paper proposes and demonstrates a highly efficient all-dielectric diatomic metasurface composed of single-crystalline Si nanocylinders and nanocubes on SiO2. This metasurface can serve as a nanoscale linear polarizer for generating polarization-angle-controllable linearly polarized light. At the wavelength of 2172 nm, the maximum transmission efficiency, extinction ratio, and linear polarization degree can reach 93.43%, 45.06 dB, and 0.9973, respectively. Moreover, a nonpolarizing beam splitter (NPBS) was designed and deduced theoretically based on this polarizer, which can achieve a splitting angle of ±13.18° and a phase difference of π. This beam splitter can be equivalently represented as an integration of a linear polarizer with controllable polarization angles and an NPBS with one-bit phase modulation. It is envisaged that through further design optimization, the phase tuning range of the metasurface can be expanded, allowing for the extension of the operational wavelength into the mid-wave infrared range, and the splitting angle is adjustable. Moreover, it can be utilized for integrated polarization detectors and be a potential application for optical digital encoding metasurfaces.

A Novel Catheter Shape-Sensing Method Based on Deep Learning with a Multi-Core Optical Fiber.

In this paper, we propose a novel shape-sensing method based on deep learning with a multi-core optical fiber for the accurate shape-sensing of catheters and guidewires. Firstly, we designed a catheter with embedded multi-core fiber containing three sensing outer cores and one temperature compensation middle core. Then, we analyzed the relationship between the central wavelength shift, the curvature of the multi-core Fiber Bragg Grating (FBG), and temperature compensation methods to establish a Particle Swarm Optimization (PSO) BP neural network-based catheter shape sensing method. Finally, experiments were conducted in both constant and variable temperature environments to validate the method. The average and maximum distance errors of the PSO-BP neural network were 0.57 and 1.33 mm, respectively, under constant temperature conditions, and 0.36 and 0.96 mm, respectively, under variable temperature conditions. This well-sensed catheter shape demonstrates the effectiveness of the shape-sensing method proposed in this paper and its potential applications in real surgical catheters and guidewire.

Tregs defects caused delayed hypersensitivity reactions to multiple disinfectants following with debridement: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Following debridement, the skin and mucous membranes around the wound must be disinfected with broad-spectrum disinfectants like Iodophor, 75 % ethanol, chlorhexidine, and bromogeramine. Despite the fact that it is rarely reported, skin allergy to disinfectants is extremely detrimental to wound recovery after debridement. CASE PRESENTATION: In this study, a 29-year-old man with no previous allergic history developed delayed contact dermatitis after being exposed to multiple disinfectants, including iodophor, 75 % ethanol, and Erythromycin ointment. Given the possibility of the patient's allergic constitution, skin patch tests were repeated to confirm the allergic disinfectants. To avoid the allergy, the wound was simply rinsed with 0.9 % sodium chloride solution and Cefdinir (0.1 g, tid) was taken orally, while all local disinfectants were discontinued. The wound healing process was gradually accelerated, and allergic symptoms were alleviated. Furthermore, our findings revealed that the frequency and immunosuppressive function of Tregs were significantly lower in patients than in healthy controls (P < 0.05). CLINICAL DISCUSSION: By minimizing allergic reactions and providing appropriate wound care, the use of 0.9 % sodium chloride solution with oral antibiotics could expedite the healing process. This enabled the wound to close faster and reduces the risk of complications. CONCLUSION: The use of 0.9 % sodium chloride solution for wound irrigation, combined with oral administration of antibiotics, could be modified to mitigate further allergic reactions and enhance the recovery process following debridement. However, individual patient characteristics and medical history should also be taken into consideration when making these alterations.

Use of left atrial automated functional myocardial imaging to identify patients with paroxysmal atrial fibrillation at high risk of stroke.

Background: Left atrial automated functional myocardial imaging (AFILA) is a new software program for analyzing the structure and function of the left atrium (LA). The present study sought to analyze the correlation between the LA function parameters as measured by AFILA echocardiography and the risk of cerebral ischemic stroke (CIS) in patients with non-valvular paroxysmal atrial fibrillation (NVPAF) to explore the diagnostic value of LA strain in patients with congestive heart failure, hypertension, age of ≥75 years (doubled), diabetes mellitus, stroke or transient ischemic attack (TIA) (doubled), age of 65-74 years, and sex category (female) (CHA2DS2-VASc) scores of <2. Methods: A total of 205 patients with NVPAF were included in the study and divided into the no-CIS group (154 patients) and the CIS group (51 patients). The baseline clinical data for the 2 groups were analyzed, and routine echocardiography examinations were performed. AFILA was used to evaluate the LA function of all the patients. Results: Compared to the no-CIS group, the LA emptying fraction and the LA reservoir strain were decreased, the LA contractile strain (S_CT) was increased, and the S_CT value changed from negative to positive in the CIS group, and the difference between the 2 groups were statistically significant (P<0.001). However, there were no significant differences in the volume at the onset of LA contraction, LA evacuation volume, LA minimum volume, LA maximum volume, and LA conduit strain between the 2 groups. The multifactorial regression analysis showed that age, hypertension, and the S_CT were independently associated risk factors for patients with CIS. After correcting for the clinical factors included in the CHA2DS2-VASc score, the S_CT was shown to predict to NVPAF with stroke [odds ratio (OR): 1.234, 95% confidence interval (CI): 1.101-1.383, P=0.000]. In addition, we included the CHA2DS2-VASc score (instead of age, diabetes, coronary artery disease, and hypertension) in a multiple regression analysis, and found that the S_CT was still significant (OR: 1.252, 95% CI: 1.118-1.402, P=0.000). The difference between the 2 groups in the CHA2DS2-VASc score for the S_CT was statistically significant, especially when the CHA2DS2-VASc score was <2. The S_CT equaled -4.5% was the cut-off value for the presence or absence of CIS in the NVPAF patients, with an area under the curve (AUC) of 0.866, sensitivity of 0.80, and specificity of 0.75 (P<0.0001). Conclusions: Comparison with LA volume parameter, measuring LA strain by AFILA provides a better index for the dynamic assessment of impaired LA function in patients with NVPAF combined with CIS, especially in those with a CHA2DS2-VASc score of <2. In addition, a LA S_CT of >-4.5% is a valuable cut-off for patients with NVPAF. The results of the current study may form the basis for a large prospective multicenter interventional study in which patients with impaired LA S_CT are randomized to receive oral anti-coagulant (OAC) therapy or no OAC therapy for the primary prevention of stroke.

Design, Synthesis, and Bioassay for the Thiadiazole-Bridged Thioacetamide Compound as Cy-FBP/SBPase Inhibitors Based on Catalytic Mechanism Virtual Screening.

Cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase (Cy-FBP/SBPase) was an important regulatory enzyme in cyanobacterial photosynthesis and was a potential target enzyme for screening to obtain novel inhibitors against cyanobacterial blooms. In this study, we developed a novel pharmacophore screening model based on the catalytic mechanism and substrate structure of Cy-FBP/SBPase and screened 26 S series compounds with different structures and pharmacophore characteristics from the Specs database by computer-assisted drug screening. These compounds exhibited moderate inhibitory activity against Cy-FBP/SBPase, with 9 compounds inhibiting >50% at 100 µM. Among them, compound S5 showed excellent inhibitory activity against both Cy-FBP/SBPase and Synechocystis sp. PCC6803 (IC50 = 6.7 ± 0.7 µM and EC50 = 7.7 ± 1.4 µM). The binding mode of compound S5 to Cy-FBP/SBPase was predicted using the molecular docking theory and validated by sentinel mutation and enzyme activity analysis. Physiochemical, gene transcription level, and metabolomic analyses showed that compound S5 significantly reduced the quantum yield of photosystem II and the maximum electron transfer rate, downregulated transcript levels of related genes encoding the Calvin cycle and photosystem, reduced the photosynthetic efficiency of cyanobacteria, thus inhibited metabolic pathways, such as the Calvin cycle and tricarboxylic acid cycle, and eventually achieved an efficient algicide. In addition, compound S5 had a high safety profile for human-derived cells and zebrafish. In summary, the novel pharmacophore screening model obtained from the current work provides an effective solution to the cyanobacterial bloom problem.

Current Discoveries and Future Implications of Eating Disorders.

Eating disorders (EDs) are characterized by severe disturbances in eating behaviors and can sometimes be fatal. Eating disorders are also associated with distressing thoughts and emotions. They can be severe conditions affecting physical, psychological, and social functions. Preoccupation with food, body weight, and shape may also play an important role in the regulation of eating disorders. Common eating disorders have three major types: anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). In some cases, EDs can have serious consequences for an individual's physical and mental health. These disorders often develop during adolescence or early adulthood and affect both males and females, although they are more commonly diagnosed in young adult females. Treatment for EDs typically involves a combination of therapy, nutrition counseling, and medical care. In this narrative review, the authors summarized what is known of EDs and discussed the future directions that may be worth exploring in this emerging area.

Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia.

Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons - namely, glucose-inhibited (GI) neurons - paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood glucose and impaired counterregulatory responses during hypoglycemia in mice. Activation of VMHAno4 neurons increased food intake and blood glucose, while chronic inhibition of VMHAno4 neurons ameliorated hyperglycemia in a type 1 diabetic mouse model. Finally, we showed that VMHAno4 neurons represent a unique orexigenic VMH population and transmit a positive valence, while stimulation of neurons that do not express Ano4 in the VMH (VMHnon-Ano4) suppress feeding and transmit a negative valence. Together, our results indicate that the Ano4 channel and VMHAno4 neurons are potential therapeutic targets for human diseases with abnormal feeding behavior or glucose imbalance.

Lewis-Base-Catalyzed Enantioselective Formal [4 + 2] Annulations of Morita-Baylis-Hillman Carbonates: Access to Tetrahydroquinolines Derivatives.

The Lewis-base-catalyzed enantioselective formal [4 + 2] annulation reaction of o-acylamino-aryl MBH carbonates and electron-deficient olefins was developed. Tetrahydroquinolines with three sequential stereogenic centers containing a quaternary stereocenter were obtained in high yields with good enantioselectivity.

Naringenin and ß-carotene convert human white adipocytes to a beige phenotype and elevate hormone- stimulated lipolysis.

Introduction: Naringenin, a peroxisome proliferator-activated receptor (PPAR) activator found in citrus fruits, upregulates markers of thermogenesis and insulin sensitivity in human adipose tissue. Our pharmacokinetics clinical trial demonstrated that naringenin is safe and bioavailable, and our case report showed that naringenin causes weight loss and improves insulin sensitivity. PPARs form heterodimers with retinoic-X-receptors (RXRs) at promoter elements of target genes. Retinoic acid is an RXR ligand metabolized from dietary carotenoids. The carotenoid ß-carotene reduces adiposity and insulin resistance in clinical trials. Our goal was to examine if carotenoids strengthen the beneficial effects of naringenin on human adipocyte metabolism. Methods: Human preadipocytes from donors with obesity were differentiated in culture and treated with 8µM naringenin + 2µM ß-carotene (NRBC) for seven days. Candidate genes involved in thermogenesis and glucose metabolism were measured as well as hormone-stimulated lipolysis. Results: We found that ß-carotene acts synergistically with naringenin to boost UCP1 and glucose metabolism genes including GLUT4 and adiponectin, compared to naringenin alone. Protein levels of PPARα, PPARγ and PPARγ-coactivator-1α, key modulators of thermogenesis and insulin sensitivity, were also upregulated after treatment with NRBC. Transcriptome sequencing was conducted and the bioinformatics analyses of the data revealed that NRBC induced enzymes for several non-UCP1 pathways for energy expenditure including triglyceride cycling, creatine kinases, and Peptidase M20 Domain Containing 1 (PM20D1). A comprehensive analysis of changes in receptor expression showed that NRBC upregulated eight receptors that have been linked to lipolysis or thermogenesis including the ß1-adrenergic receptor and the parathyroid hormone receptor. NRBC increased levels of triglyceride lipases and agonist-stimulated lipolysis in adipocytes. We observed that expression of RXRγ, an isoform of unknown function, was induced ten-fold after treatment with NRBC. We show that RXRγ is a coactivator bound to the immunoprecipitated PPARγ protein complex from white and beige human adipocytes. Discussion: There is a need for obesity treatments that can be administered long-term without side effects. NRBC increases the abundance and lipolytic response of multiple receptors for hormones released after exercise and cold exposure. Lipolysis provides the fuel for thermogenesis, and these observations suggest that NRBC has therapeutic potential.