Loss of transient receptor potential channel 5 causes obesity and postpartum depression.

Hypothalamic neural circuits regulate instinctive behaviors such as food seeking, the fight/flight response, socialization, and maternal care. Here, we identified microdeletions on chromosome Xq23 disrupting the brain-expressed transient receptor potential (TRP) channel 5 (TRPC5). This family of channels detects sensory stimuli and converts them into electrical signals interpretable by the brain. Male TRPC5 deletion carriers exhibited food seeking, obesity, anxiety, and autism, which were recapitulated in knockin male mice harboring a human loss-of-function TRPC5 mutation. Women carrying TRPC5 deletions had severe postpartum depression. As mothers, female knockin mice exhibited anhedonia and depression-like behavior with impaired care of offspring. Deletion of Trpc5 from oxytocin neurons in the hypothalamic paraventricular nucleus caused obesity in both sexes and postpartum depressive behavior in females, while Trpc5 overexpression in oxytocin neurons in knock-in mice reversed these phenotypes. We demonstrate that TRPC5 plays a pivotal role in mediating innate human behaviors fundamental to survival, including food seeking and maternal care.

Extracellular Vesicle-Mediated Neuron-Glia Communications in the Central Nervous System.

Communication between neurons and glia significantly influences the development maturation, plasticity, and disease progressions of the nervous system. As a new signaling modality, extracellular vesicles display a diverse role for robust functional regulation of neurons through their protein and nucleic acid cargoes. This review highlights recent breakthroughs in the research of signaling mechanisms between glia and neurons mediated by extracellular vesicles that are important for neural development, axonal maintenance, synaptic functions, and disease progression in the mammalian nervous system. We will discuss the biological roles of extracellular vesicles released from neurons, astroglia, microglia, and oligodendroglia in the nervous system and their implications in neurodegenerative disorders.

A Light-Responsive Neural Circuit Suppresses Feeding.

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb→5-HTDRN circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light-responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice.

All-fiber tunable mode converter for a mini-two-arm Mach-Zehnder interferometer.

In this Letter, an all-fiber tunable mode converter for a mini-two-arm Mach-Zehnder interferometer (MTA-MZI) is proposed and realized for the first time to our knowledge. Employing an electric arc discharge technology, we couple a multi-mode fiber (MMF) and a single-mode fiber (SMF), resulting in an MZI characterized by centimeter-scale arms. The varied sensitivity of fiber modes to curvature makes the high-order modes of the MMF more prone to leakage when subjected to bending, leading to alterations in the output interference fringe pattern of the MZI. Through continuous monitoring of the interference fringes of the MZI, we effectively detect the mode properties within the MZI in real time. In addition, a verification experiment is conducted by introducing a peanut structure to excite further higher-order modes of light to enter the MZI in advance. Upon modifying the curvature of the MZI, these excited higher-order modes leak, causing the interference fringe pattern to revert to its initial state without a peanut structure. This experimental validation highlights the potential employment of the MTA-MZI as an all-fiber mode converter and paves the way for optical field mode conversion within an all-fiber framework.

Visual fluorescence detection of Listeria monocytogenes with CRISPR-Cas12a aptasensor.

Listeria monocytogenes (L. monocytogenes) is a prevalent food-borne pathogen that can cause listeriosis, which manifests as meningitis and other symptoms, potentially leading to fatal outcomes in severe cases. In this study, we developed an aptasensor utilizing carboxylated magnetic beads and Cas12a to detect L. monocytogenes. In the absence of L. monocytogenes, the aptamer maintains its spatial configuration, keeping the double-stranded DNA attached and preventing the release of a startup template and activation of Cas12a's trans-cleavage capability. Conversely, in the presence of L. monocytogenes, the aptamer undergoes a conformational change, releasing the double-stranded DNA to serve as a startup template, thereby activating the trans-cleavage capability of Cas12a. Consequently, as the concentration of L. monocytogenes increases, the observable brightness in a blue light gel cutter intensifies, leading to a rise in fluorescence intensity difference compared to the control. This Cas12a aptasensor demonstrates excellent sensitivity towards L. monocytogenes, with a lowest detection limit (LOD) of 57.15 CFU/mL and a linear range of 4×102 to 4×107 CFU/mL (R2=0.9858). Notably, the proposed Cas12a aptasensor exhibited outstanding selectivity and recovery in beef samples, and could be employed for precise monitoring. This Cas12a aptasensor not only provides a novel fluorescent and visual rapid detection method for L. monocytogenes but also offers simplicity, speed, and stability compared to previous detection methods. Furthermore, it is suitable for on-site detection of beef samples.

ACE2 mediates tryptophan alleviation on diarrhea by repairing intestine barrier involved mTOR pathway.

The membrane-delimited receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2 (ACE2), which is expressed in the intestine, collaborates with broad neutral amino acid transporter 1 (B0AT1). Tryptophan (Trp) is transported into intestinal epithelial cells by ACE2 and B0AT1. However, whether ACE2 and its binding protein B0AT1 are involved in Trp-mediated alleviation of intestinal injury is largely unknown. Here, we used weaned piglets and IPEC-J2 cells as models and found that ACE2/B0AT1 alleviated lipopolysaccharide (LPS)-induced diarrhea and promoted intestinal barrier recovery via transport of Trp. The levels of the aryl hydrocarbon receptor (AhR) and mechanistic target of rapamycin (mTOR) pathways were altered by ACE2. Dietary Trp supplementation in LPS-treated weaned piglets revealed that Trp alleviated diarrhea by promoting ACE2/B0AT1 expression, and examination of intestinal morphology revealed that the damage to the intestinal barrier was repaired. Our study demonstrated that ACE2 accompanied by B0AT1 mediated the alleviation of diarrhea by Trp through intestinal barrier repair via the mTOR pathway.

Nursing-sensitive Indicators for Quality Improvement for Patients with Traumatic Brain Injury.

Context: Traumatic brain injury (TBI) can result in lifelong cognitive, emotional, and motor impairments. The emergency department is the first stop for diagnosing and treating patients with acute TBI, and the quality of nursing care can greatly influence the prognosis and progression of a patient's condition. Currently, standardized evaluation tools are lacking in the world for assessment of the quality of nursing care. Objective: The study intended to construct a nursing-sensitive indicator system for TBI patients, based on the scientific method of evidence-based nursing and the Delphi method, to provide a quantitative tool for emergency-nursing personnel to manage the quality of care for those patients. Design: Based on the Joanna Briggs Institute's evidence-based healthcare model, the research team performed a literature search and consulted reference guidelines, conducted two rounds of consultations with experts. sensitive indicators for quality of care, and constructed the sensitive indicator system. The team then conducted a retrospective study. Setting: The study took place in the department of emergency surgery at Shanxi Norman Bethune Hospital in Taiyuan, Shanxi, China. Participants: Participants were 56 patients with TBI who had been admitted to the emergency department between January 2022 and December 2022 and 44 patients with TBI who had been admitted to the emergency department between January 2023 and December 2023. Interventions: The research team assigned: (1) the 56 patients in the first group to the control group, who received routine nursing care and (2) the 44 patients in the second group to the intervention group, who received treatment using the sensitive indicator system for the quality of emergency care for TBI patients as well as routine care. Outcome Measures: In the verification study, the research team compared the group's rescue effects and satisfaction with emergency care. Results: In the first and second rounds of inquiries to experts, the research team distributed 25 questionnaires each time, with 25 valid questionnaires collected both times. The response rate for both rounds of inquiries was 100%. The expert authority coefficients for the first and second rounds of inquiries are 0.844 and 0.878, respectively. The sensitive indicator system's final construction included three primary indicators, seven secondary indicators, and 17 tertiary indicators. The AUC for the sensitive indicators was 0.8355882. The indicator system's use found that the intervention group had a shorter time to diagnosis (P < .001), emergency-department stay (P < .001), and emergency-department-to-surgery time (P < .001) compared to the control group. The intervention group also has a higher success rate for the emergency treatment (P = .014) and a higher nursing satisfaction with nurse-patient communications (P = .003), first-aid operations (P < .001), nursing attitudes (P < .001), and emergency environment (P < .001) compared to the control group. Conclusions: The process of constructing quality-sensitive indicators for the nursing care of TBI patients was scientific. The constructed quality-sensitive indicator system for the care of patients with TBI covers key factors that influence the quality of care. It's highly practical and has the ability to transform certain indicators, which can better guide the management of quality of care for TBI.

Seven oral traditional Chinese medicine combined with chemotherapy for the treatment of non-small cell lung cancer: a network meta-analysis.

CONTEXT: Traditional Chinese medicines (TCMs) have emerged as potential adjuvant therapies to treat non-small cell lung cancer. More direct comparative studies must be conducted among various oral TCMs. OBJECTIVE: This network meta-analysis evaluates the efficacy and safety of seven oral TCMs combined with chemotherapy in treating NSCLC. METHODS: The analysis included Zilongjin, Banmao, Hongdoushan, Huachansu, Kanglaite, Xihuang, and Pingxiao TCMs. Randomized-controlled trials (RCTs) were identified from the following databases: China National Infrastructure, Wanfang, PubMed, Embase, and the Cochrane Library up to April 2023. Two researchers independently extracted data. RESULTS: Sixty-eight RCTs (5,099 patients) were included. Compared to chemotherapy, Banmao capsules [odds ratio (OR) = 2.69, 95% confidence interval (CI) 1.96-3.69)] and Huachansu tablets [OR = 2.35, 95%CI (1.81, 3.05)] ranked in the top two in terms of increasing disease control rate. The two main TCMs to improve the objective response rate were Banmao capsules [OR = 3.49, 95%CI (2.17, 5.60)] and Zilongjin tablets [OR = 2.62, 95%CI (1.92, 3.57)]. Zilongjin tablets [OR = 3.47, 95%CI (2.14, 5.63)] and Huachansu tablets [OR = 3.30, 95%CI (1.65, 6.60)] were ranked as the top two in improving Karnofsky performance status. Hongdoushan capsules (SUCRA = 18.8%) and Banmao capsules (SUCRA = 19.8%) were the top two in reducing gastrointestinal toxicity. Zilongjin tablets (SUCRA = 18.9%) and Banmao capsules (SUCRA = 26.6%) were the top two to reduce liver and kidney toxicity. Hongdoushan capsules (SUCRA = 15.7%) and Huachansu tablets (SUCRA = 16.8%) ranked the top two in reducing thrombocytopenia. Banmao capsules (SUCRA = 14.3%) and Zilongjin tablets (SUCRA = 26.3%) were the top two decreasing leukopenia. CONCLUSIONS: Combining oral TCMs with platinum-based chemotherapy has shown superior efficacy compared to platinum-based chemotherapy alone in treating NSCLC.

Functionally Clustered mRNAs Are Distinctly Enriched at Cortical Astroglial Processes and Are Preferentially Affected by FMRP Deficiency.

Mature protoplasmic astroglia in the mammalian CNS uniquely possess a large number of fine processes that have been considered primary sites to mediate astroglia to neuron synaptic signaling. However, localized mechanisms for regulating interactions between astroglial processes and synapses, especially for regulating the expression of functional surface proteins at these fine processes, are largely unknown. Previously, we showed that the loss of the RNA binding protein FMRP in astroglia disrupts astroglial mGluR5 signaling and reduces expression of the major astroglial glutamate transporter GLT1 and glutamate uptake in the cortex of Fmr1 conditional deletion mice. In the current study, by examining ribosome localization using electron microscopy and identifying mRNAs enriched at cortical astroglial processes using synaptoneurosome/translating ribosome affinity purification and RNA-Seq in WT and FMRP-deficient male mice, our results reveal interesting localization-dependent functional clusters of mRNAs at astroglial processes. We further showed that the lack of FMRP preferentially alters the subcellular localization and expression of process-localized mRNAs. Together, we defined the role of FMRP in altering mRNA localization and expression at astroglial processes at the postnatal development (P30-P40) and provided new candidate mRNAs that are potentially regulated by FMRP in cortical astroglia.SIGNIFICANCE STATEMENT Localized mechanisms for regulating interactions between astroglial processes and synapses, especially for regulating the expression of functional surface proteins at these fine processes, are largely unknown. Previously, we showed that the loss of the RNA binding protein FMRP in astroglia disrupts expression of several astroglial surface proteins, such as mGluR5 and major astroglial glutamate transporter GLT1 in the cortex of FMRP-deficient mice. Our current study examined ribosome localization using electron microscopy and identified mRNAs enriched at cortical astroglial processes in WT and FMRP-deficient mice. These results reveal interesting localization-dependent functional clusters of mRNAs at astroglial processes and demonstrate that the lack of FMRP preferentially alters the subcellular localization and expression of process-localized mRNAs.

Chronic nSMase inhibition suppresses neuronal exosome spreading and sex-specifically attenuates amyloid pathology in APP knock-in Alzheimer's disease mice.

Female biased pathology and cognitive decline in Alzheimer's disease (AD) have been consistently observed with unclear underlying mechanisms. Although brain sphingolipid ceramide is elevated in AD patients, whether and how ceramide may contribute to sex-specific differences in amyloid pathology is unknown. Here we investigated the sex-specific impact of chronic pharmacological inhibition of neutral sphingomyelinase (nSMase), a key enzyme responsible for ceramide metabolism, on in vivo neuron-derived exosome dynamics, Aß plaque load, and cognitive function in the APPNL-F/NL-F knock-in (APP NL-F) AD mouse model. Our results found sex-specific increase of cortical C20:0 ceramide and brain exosome levels only in APP NL-F but not in age-matched WT mice. Although nSMase inhibition similarly blocks exosome spreading in male and female mice, significantly reduced amyloid pathology was mostly observed in cortex and hippocampus of female APP NL-F mice with only modest effect found on male APP NL-F mice. Consistently, T maze test to examine spatial working memory revealed a female-specific reduction in spontaneous alternation rate in APP NL-F mice, which was fully reversed with chronic nSMase inhibition. Together, our results suggest that disease induced changes in ceramide and exosome pathways contribute to the progression of female-specific amyloid pathology in APP NL-F AD models.

Trending prevalence of healthcare-associated infections in a tertiary hospital in China during the COVID-19 pandemic.

BACKGROUND: The purpose of this study was to demonstrate both the four-year prevalence trend of healthcare-associated infections (HAIs) in a large tertiary hospital and the trend regarding the prevalence of HAIs following the outbreak of coronavirus disease 2019 (COVID-19) in order to provide evidence of hospital infection management during the COVID-19 pandemic. METHODS: Based on the hospital's electronic nosocomial infection databases related to HAIs, we retrospectively identified the HAI cases to assess the epidemiological characteristics of HAIs from January 1, 2018, to December 31, 2021, in a large tertiary hospital in China. Similarly, the trends of HAIs after the COVID-19 outbreak and the seasonal variation of HAIs were further analyzed. RESULTS: The HAI cases (n = 7833) were identified from the inpatients (n = 483,258) during the 4 years. The most frequently occurring underlying cause of HAIs was respiratory tract infections (44.47%), followed by bloodstream infections (11.59%), and urinary tract infections (8.69%). The annual prevalence of HAIs decreased from 2.39% in 2018 to 1.41% in 2021 (P = 0.032), with the overall prevalence of HAIs significantly decreasing since the outbreak of COVID-19 (2.20% in 2018-2019 vs. 1.44% in 2020-2021, P < 0.001). The prevalence of respiratory tract infections decreased most significantly; whereas, overall, the prevalence of HAIs was significantly greater during the winter compared with the rest of the year. CONCLUSIONS: Not only did the annual prevalence of HAIs decrease from 2018 to 2021, but it also significantly decreased since the start of the COVID-19 pandemic, particularly respiratory tract infections. These results provide evidence for the need to prevent HAIs, especially during the winter season.

Highly sensitive temperature and refractive index sensor based on no-core fiber cascaded with a balloon-shaped bent single-mode fiber.

A highly sensitive temperature and refractive index (RI) sensor based on no-core fiber (NCF) cascaded with a balloon-shaped bent single-mode fiber (BSBSF) is proposed and demonstrated. The NCF can excite higher-order modes which will be concentrated and transmitted into the BSBSF due to the characteristic of self-imaging effect. The BSBSF has an excellent temperature performance due to the high thermo-optical coefficient and thermal expansion coefficient of the polymer coating. The NCF and BSBSF are both conducive to the excitation of higher-order modes, which induces the sensitivity of the sensor with an efficiency improvement. The experimental results show that the maximum temperature sensitivity is -3.19n m/ ∘ C in the range of 22°C-83°C, which is the highest temperature sensitivity in the cascaded BSBSF structure to our best knowledge. In addition, the maximum RI sensitivity is 232.16 nm/RIU when the RI changes from 1.3234 to 1.3512. Compared with other cascaded BSBSF structures, this sensor has a higher temperature sensitivity and can be applicated in the prospects of food, biology, and environmental monitoring.

Astroglial FMRP deficiency cell-autonomously up-regulates miR-128 and disrupts developmental astroglial mGluR5 signaling.

The loss of fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), the most common inherited intellectual disability. How the loss of FMRP alters protein expression and astroglial functions remains essentially unknown. Here we showed that selective loss of astroglial FMRP in vivo up-regulates a brain-enriched miRNA, miR-128-3p, in mouse and human FMRP-deficient astroglia, which suppresses developmental expression of astroglial metabotropic glutamate receptor 5 (mGluR5), a major receptor in mediating developmental astroglia to neuron communication. Selective in vivo inhibition of miR-128-3p in FMRP-deficient astroglia sufficiently rescues decreased mGluR5 function, while astroglial overexpression of miR-128-3p strongly and selectively diminishes developmental astroglial mGluR5 signaling. Subsequent transcriptome and proteome profiling further suggests that FMRP commonly and preferentially regulates protein expression through posttranscriptional, but not transcriptional, mechanisms in astroglia. Overall, our study defines an FMRP-dependent cell-autonomous miR pathway that selectively alters developmental astroglial mGluR5 signaling, unveiling astroglial molecular mechanisms involved in FXS pathogenesis.

Study on the Effectiveness and Value of Evidence-Based Nursing and Predictive Nursing in Emergency Treatment of Upper Gastrointestinal Bleeding.

Objective: To study the effectiveness and value of evidence-based nursing and predictive nursing in emergency treatment of upper gastrointestinal bleeding. Methods: A total of 100 patients with upper gastrointestinal bleeding in our hospital were selected. The period was from January 2020 to June 2022. They were grouped according to the double color ball method, 50 cases in the control group were given routine nursing, and 50 cases in the observation group were given evidence-based nursing combined with predictive nursing. The key points of evidence-based nursing are to identify the evidence-based question, search for relevant literature, identify scientifically effective nursing measures, and develop nursing care plans that are tailored to the patient's specific situation based on evidence and clinical experience. Predictive nursing requires nurses to have a high level of awareness and risk prevention consciousness to provide care for early signs of bleeding and prevent the occurrence of complications. The psychological state scores, clinical-related indicators, clinical efficacy, incidence of complications, nursing satisfaction, and quality of life scores of the two groups were compared. Results: After the intervention, the SAS score (42.25 ± 1.67) and SDS score (43.59 ± 1.86) of the observation group were lower than those of the control group, the bleeding times (2.41 ± 0.45) of the observation group were less than those of the control group, the hemostasis time (30.12 ± 5.38d) and hospitalization time (5.01 ± 1.11d) of the observation group were shorter than those of the control group, and the difference was statistically significant (all P < .05). The total effective rate of hemostasis (96.00%), patient satisfaction (98.00%), and scores of physical health (88.98 ± 5.59), psychological function (91.08 ± 5.11), material life state (90.54 ± 6.46) and social function (89.59 ± 5.78) in GQOLI-74 scores in the observation group were higher than those in the control group. The incidence of complications (6.00%) in the observation group was lower than that in the control group, and the difference was statistically significant (all P < .05). Conclusion: Upper gastrointestinal bleeding is a common emergency in gastroenterology, characterized by rapid onset, severe symptoms, and quick changes. Therefore, in order to expedite the recovery of patients with acute upper gastrointestinal bleeding and ensure their safety, it is necessary to provide effective clinical emergency nursing care. Evidence-based nursing can help nurses take appropriate nursing measures based on the best and latest evidence, to meet the reasonable individualized needs of patients. Predictive nursing is a nursing model that predicts potential nursing risks in advance and takes corresponding preventive measures. It can timely and systematically address risks in nursing and promote improvements in the effectiveness of disease treatment. The combined application of evidence-based nursing and predictive nursing can improve the hemostatic efficiency of patients with upper gastrointestinal bleeding, improve the psychological state and quality of life, reduce the incidence of complications, and obtain higher satisfaction. The combined application of these two nursing models has positive implications for improving nursing efficiency, enhancing patient cooperation during emergency care, improving hemostasis effectiveness, enhancing quality of life, and fostering a harmonious nurse-patient relationship.

Real-Time LiDAR Point-Cloud Moving Object Segmentation for Autonomous Driving.

The key to autonomous navigation in unmanned systems is the ability to recognize static and moving objects in the environment and to support the task of predicting the future state of the environment, avoiding collisions, and planning. However, because the existing 3D LiDAR point-cloud moving object segmentation (MOS) convolutional neural network (CNN) models are very complex and have large computation burden, it is difficult to perform real-time processing on embedded platforms. In this paper, we propose a lightweight MOS network structure based on LiDAR point-cloud sequence range images with only 2.3 M parameters, which is 66% less than the state-of-the-art network. When running on RTX 3090 GPU, the processing time is 35.82 ms per frame and it achieves an intersection-over-union(IoU) score of 51.3% on the SemanticKITTI dataset. In addition, the proposed CNN successfully runs the FPGA platform using an NVDLA-like hardware architecture, and the system achieves efficient and accurate moving-object segmentation of LiDAR point clouds at a speed of 32 fps, meeting the real-time requirements of autonomous vehicles.

Intelligent Hotel Guidance System via Face Recognition Technology.

In modern large hotels, due to a large number of rooms and complex layouts, it is difficult for customers to find rooms, which increases a lot of workloads for hotel attendants to guide. In this paper, a hotel intelligent guidance system based on face recognition is designed. After entering the customer's facial photos, the room guidance and customer management are carried out through face recognition. With this, hotels can move toward card-free management, green environmental protection, and save on resources. With these improvements, hotel management will be card-free and green. Each monitoring device of the system adopts dual STM32 core architecture, in which STM32H7 is responsible for face recognition, while STM32L4 is the main control chip, which is responsible for data exchange, guest room guidance and other work. The monitoring master not only guides, but also uploads customer check-in information to the cloud platform to facilitate the management of the hotel. The system adopts contactless information collection and guidance, which improves the intelligence and humanization of the hotel, and has a good application prospect.

Barbadin Potentiates Long-Term Effects of Lorcaserin on POMC Neurons and Weight Loss.

Obesity is a serious global health problem because of its increasing prevalence and comorbidities, but its treatments are limited. The serotonin 2C receptor (5-HT2CR), a G-protein-coupled receptor, activates proopiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus (ARH) to reduce appetite and weight gain. However, several 5-HT analogs targeting this receptor, e.g., lorcaserin (Lor), suffer from diminished efficacy to reduce weight after prolonged administration. Here, we show that barbadin (Bar), a novel ß-arrestin/ß2-adaptin inhibitor, can prevent 5-HT2CR internalization in cells and potentiate long-term effects of Lor to reduce appetite and body weight in male mice. Mechanistically, we demonstrate that Bar co-treatment can effectively maintain the sensitivity of the 5-HT2CR in POMCARH neurons, despite prolonged Lor exposure, thereby allowing these neurons to be activated through opening the transient receptor potential cation (TRPC) channels. Thus, our results prove the concept that inhibition of 5-HT2CR desensitization can be a valid strategy to improve the long-term weight loss effects of Lor or other 5-HT2CR agonists, and also provide an intellectual framework to develop effective long-term management of weight by targeting 5-HT2CR desensitization.SIGNIFICANCE STATEMENT By demonstrating that the combination of barbadin (Bar) with a G-protein-coupled receptor (GPCR) agonist can provide prolonged weight-lowering benefits in a preclinical setting, our work should call for additional efforts to validate Bar as a safe and effective medicine or to use Bar as a lead compound to develop more suitable compounds for obesity treatment. These results prove the concept that inhibition of serotonin 2C receptor (5-HT2CR) desensitization can be a valid strategy to improve the long-term weight loss effects of lorcaserin (Lor) or other 5-HT2CR agonists. Since GPCRs represent a major category as therapeutic targets for various human diseases and desensitization of GPCRs is a common issue, our work may provide a conceptual framework to enhance effects of a broad range of GPCR medicines.

Selection and characterization of bispecific aptamers against malachite green and leucomalachite green.

In order to develop multi-residues rapid detection, the bispecific aptamers against malachite green (MG) and leucomalachite green (LMG) were isolated by the capture systematic evolution of ligands by exponential enrichment (Capture-SELEX). After thirteen rounds of selection, the enriched ssDNA pools were sent for high-throughput sequencing. Nine aptamer candidates (A1-A9) were picked out to test their specificity by gold nanoparticles (AuNPs) colorimetric assay. Three aptamers (A2, A3, A5) with good selectivity were truncated to verify their affinity by fluorescence assay. Finally, three truncated aptamers (A2-a, A3-a, A5-a) with bispecificity and high affinity were identified. For LMG, the dissociation constant (Kd) of them were 8.4 ± 0.8 nM, 8.2 ± 1.2 nM, and 13.7 ± 1.4 nM, respectively. For MG, Kd of them were 3.4 ± 0.3 µM, 2.3 ± 0.2 µM, 3.0 ± 0.2 µM. Among them, A3-a is the best. Our work will provide novel probes for the development of multi-residues rapid detection as well as opportunities for multiple target aptamer discovery.

5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding.

Obesity is primarily a consequence of consuming calories beyond energetic requirements, but underpinning drivers have not been fully defined. 5-Hydroxytryptamine (5-HT) neurons in the dorsal Raphe nucleus (5-HTDRN) regulate different types of feeding behavior, such as eating to cope with hunger or for pleasure. Here, we observed that activation of 5-HTDRN to hypothalamic arcuate nucleus (5-HTDRN → ARH) projections inhibits food intake driven by hunger via actions at ARH 5-HT2C and 5-HT1B receptors, whereas activation of 5-HTDRN to ventral tegmental area (5-HTDRN → VTA) projections inhibits non-hunger-driven feeding via actions at 5-HT2C receptors. Further, hunger-driven feeding gradually activates ARH-projecting 5-HTDRN neurons via inhibiting their responsiveness to inhibitory GABAergic inputs; non-hunger-driven feeding activates VTA-projecting 5-HTDRN neurons through reducing a potassium outward current. Thus, our results support a model whereby parallel circuits modulate feeding behavior either in response to hunger or to hunger-independent cues.

Cognitive-behavioral therapy on psychological stress and quality of life in subjects with pulmonary tuberculosis: a community-based cluster randomized controlled trial.

BACKGROUND: Anxiety and depression are two common psychological disorders in patients with pulmonary tuberculosis. We aimed to explore the effects of cognitive-behavioral therapy (CBT) on psychological stress and quality of life in patients with pulmonary tuberculosis. METHODS: From September 2018 to November 2018, 20 communities (461 participants in total) were randomly assigned in an intervention or control group following a two-level cluster random design. The intervention group underwent CBT for 2 months, whereas the control group received routine follow-up. Anxiety, depression, and quality of life were assessed using the Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder questionnaire (GAD-7), and 36-Item Short-Form Health Survey (SF-36) scales, respectively. Comparisons between the two groups were conducted using independent samples t-tests, and differences between the two groups before and after treatment were analyzed using paired samples t-tests. RESULTS: There were a total of 454 participants in the final analysis. After 2 months of CBT intervention, the CBT group had a GAD-7 score that was 1.72 lower than the control group (1.47-1.99, p < 0.001), a PHQ-9 score of the CBT group that was 2.05 lower than that of the control group (1.74-2.37, p < 0.001). The CBT group had a total SF-36 score that was 10.7 lower than that of the control group (95% CI: 7.9-13.5, p < 0.001). In patients with different degrees of anxiety and depression, only those in the intervention group who had mild and moderate anxiety and depression symptoms showed a significant reduction in anxiety and depression scores following the intervention. CONCLUSIONS: CBT can relieve anxiety, and depression symptoms and increase the quality of life in subjects with pulmonary tuberculosis. TRIALS REGISTRATION: ChiCTR-TRC-12001958 Date of Registration: 22/02/2012.