Denoised single-pixel imaging in a Fourier acquisition mode.

The degradation of imaging quality caused by environmental noise during Fourier single pixel imaging (FSPI) is a big problem. In this paper, we propose simple and efficient denoised single-pixel imaging schemes by using linear filters to reduce the impact. Two filters, such as an average filter and Gaussian filter, are employed, and their corresponding schemes are named SCH-A and SCH-G, respectively. The experimental and simulation results show that both schemes can effectively reduce the impact of environmental noise and have greater robustness in comparison with those using the deringing SPI and conventional SPI. Compared with SCH-A, the reconstructed image by SCH-G keeps more details and edges. With the increase of template size, SCH-A and SCH-G have better filtering effects with the same variance. Meanwhile, the larger the template size is, the better filtering effect SCH-A has. This conclusion is also applicable to SCH-G under the same variance.

Comparison of the prognostic effect of pyrotinib plus trastuzumab and chemotherapy different lines therapy in HER2-positive advanced breast cancer.

This study aimed to compare the efficacy of pyrotinib, trastuzumab combined with chemotherapy with different lines therapy in human epidermal growth factor receptor 2- (HER2-) positive advanced breast cancer (ABC) and analyze the factors affecting the prognosis. A total of 84 patients with median age of 49 year-old. The mPFS of patients receiving first-line pyrotinib plus trastuzumab and chemotherapy was the longest (11 months) compared with second- and third line patients (p = 0.106). The objective response rate (ORR) and disease control rate (DCR) of the total population were 33.3% and 82.1% respectively. Subgroup analysis suggested that using pyrotinib plus trastuzumab and Albumin-bound paclitaxel was not inferior to combine with Vinorelbine in regards of PFS. Histological grade (OR: 0.233[0.069 ∼ 0.781], p = 0.018) and tumor location (OR: 0.286[0.087 ∼ 0.942], p = 0.040) were independent factors influencing the ORR. Multivariate cox analysis showed that Ki-67 was independently associated with increased risk of progression (HR: 1.843[1.044-3.254], p = 0.035). The most common adverse events were diarrhea (17.9%) and neutropenia (11.9%). In the first-, second- and third-line treatment, pyrotinib plus trastuzumab and chemotherapy is effective and safe. Pyrotinib and trastuzumab combined with Albumin-bound paclitaxel may be a potential ideal treatment plan for HER2-positive advanced breast cancer.

Potassium channel-related epilepsy: Pathogenesis and clinical features.

Variants in potassium channel-related genes are one of the most important mechanisms underlying abnormal neuronal excitation and disturbances in the cellular resting membrane potential. These variants can cause different forms of epilepsy, which can seriously affect the physical and mental health of patients, especially those with refractory epilepsy or status epilepticus, which are common among pediatric patients and are potentially life-threatening. Variants in potassium ion channel-related genes have been reported in few studies; however, to our knowledge, no systematic review has been published. This study aimed to summarize the epilepsy phenotypes, functional studies, and pharmacological advances associated with different potassium channel gene variants to assist clinical practitioners and drug development teams to develop evidence-based medicine and guide research strategies. PubMed and Google Scholar were searched for relevant literature on potassium channel-related epilepsy reported in the past 5-10 years. Various common potassium ion channel gene variants can lead to heterogeneous epilepsy phenotypes, and functional effects can result from gene deletions and compound effects. Administration of select anti-seizure medications is the primary treatment for this type of epilepsy. Most patients are refractory to anti-seizure medications, and some novel anti-seizure medications have been found to improve seizures. Use of targeted drugs to correct aberrant channel function based on the type of potassium channel gene variant can be used as an evidence-based pathway to achieve precise and individualized treatment for children with epilepsy. PLAIN LANGUAGE SUMMARY: In this article, the pathogenesis and clinical characteristics of epilepsy caused by different types of potassium channel gene variants are reviewed in the light of the latest research literature at home and abroad, with the expectation of providing a certain theoretical basis for the diagnosis and treatment of children with this type of disease.

Enzymatic characterization and thermostability improvement of an acidophilic endoxylanase PphXyn11 from Paenibacillus physcomitrellae XB.

GH11 enzyme is known to be specific and efficient for the hydrolysis of xylan. It has been isolated from many microorganisms, and its enzymatic characteristics and thermostability vary between species. In this study, a GH11 enzyme PphXyn11 from a novel xylan-degrading strain of Paenibacillus physcomitrellae XB was characterized, and five mutants were constructed to try to improve the enzyme's thermostability. The results showed that PphXyn11 was an acidophilic endo-ß-1,4-xylanase with the optimal reaction pH of 3.0-4.0, and it could deconstruct different kinds of xylan substrates efficiently, such as beechwood xylan, wheat arabinoxylan and xylo-oligosaccharides, to produce xylobiose and xylotriose as the main products at the optimal reaction temperature of 40 °C. Improvement of the thermal stability of PphXyn11 using site-directed mutagenesis revealed that three mutants, W33C/N47C, S127C/N174C and S49E, designed by adding the disulfide bonds at the N-terminal, C-terminal and increasing the charged residues on the surface of PphXyn11 respectively, could increase the enzymatic activity and thermal stablility significantly and make the optimal reaction temperature reach 50 °C. Molecular dynamics simulations as well as computed the numbers of salt bridges and hydrogen bonds indicated that the protein structures of these three mutants were more stable than the wild type, which provided theoretical support for their improved thermal stability. Certainly, further research is necessary to improve the enzymatic characteristics of PphXyn11 to achieve the bioconversion of hemicellulosic biomass on an applicable scale.

Interpretable machine learning-based clinical prediction model for predicting lymph node metastasis in patients with intrahepatic cholangiocarcinoma.

OBJECTIVE: Prediction of lymph node metastasis (LNM) for intrahepatic cholangiocarcinoma (ICC) is critical for the treatment regimen and prognosis. We aim to develop and validate machine learning (ML)-based predictive models for LNM in patients with ICC. METHODS: A total of 345 patients with clinicopathological characteristics confirmed ICC from Jan 2007 to Jan 2019 were enrolled. The predictors of LNM were identified by the least absolute shrinkage and selection operator (LASSO) and logistic analysis. The selected variables were used for developing prediction models for LNM by six ML algorithms, including Logistic regression (LR), Gradient boosting machine (GBM), Extreme gradient boosting (XGB), Random Forest (RF), Decision tree (DT), Multilayer perceptron (MLP). We applied 10-fold cross validation as internal validation and calculated the average of the areas under the receiver operating characteristic (ROC) curve to measure the performance of all models. A feature selection approach was applied to identify importance of predictors in each model. The heat map was used to investigate the correlation of features. Finally, we established a web calculator using the best-performing model. RESULTS: In multivariate logistic regression analysis, factors including alcoholic liver disease (ALD), smoking, boundary, diameter, and white blood cell (WBC) were identified as independent predictors for LNM in patients with ICC. In internal validation, the average values of AUC of six models ranged from 0.820 to 0.908. The XGB model was identified as the best model, the average AUC was 0.908. Finally, we established a web calculator by XGB model, which was useful for clinicians to calculate the likelihood of LNM. CONCLUSION: The proposed ML-based predicted models had a good performance to predict LNM of patients with ICC. XGB performed best. A web calculator based on the ML algorithm showed promise in assisting clinicians to predict LNM and developed individualized medical plans.

State-dependent central synaptic regulation by GLP-1 is essential for energy homeostasis.

Central nervous system (CNS) control of metabolism plays a pivotal role in maintaining energy homeostasis. Glucagon-like peptide-1 (GLP-1, encoded by Gcg), secreted by a distinct population of neurons located within the nucleus tractus solitarius (NTS), suppresses feeding through projections to multiple brain targets1-3. Although GLP-1 analogs are proven clinically effective in treating type 2 diabetes and obesity4, the mechanisms of GLP-1 action within the brain remain unclear. Here, we investigate the involvement of GLP-1 receptor (GLP-1R) mediated signaling in a descending circuit formed by GLP-1R neurons in the paraventricular hypothalamic nucleus (PVNGLP-1R) that project to dorsal vagal complex (DVC) neurons of the brain stem in mice. PVNGLP- 1R→DVC synapses release glutamate that is augmented by GLP-1 via a presynaptic mechanism. Chemogenetic activation of PVNGLP-1R→DVC neurons suppresses feeding. The PVNGLP-1R→DVC synaptic transmission is dynamically regulated by energy states. In a state of energy deficit, synaptic strength is weaker but is more profoundly augmented by GLP-1R signaling compared to an energy-replete state. In an obese state, the dynamic synaptic strength changes in the PVNGLP-1R→DVC descending circuit are disrupted. Blocking PVNGLP-1R→DVC synaptic release or ablation of GLP-1R in the presynaptic compartment increases food intake and causes obesity, elevated blood glucose, and impaired insulin sensitivity. These findings suggest that the state-dependent synaptic plasticity in this PVNGLP-1R→DVC descending circuit mediated by GLP-1R signaling is an essential regulator of energy homeostasis.

Liraglutide Protects Pancreatic Islet From Ischemic Injury by Reducing Oxidative Stress and Activating Akt Signaling During Cold Preservation to Improve Islet Transplantation Outcomes.

BACKGROUND: Islet transplantation is a promising therapy for patients with type 1 diabetes. However, ischemic injury to the donor islets during cold preservation leads to reduced islet quality and compromises transplant outcome. Several studies imply that liraglutide, a glucagon-like peptide-1 receptor agonist, has a positive effect on promoting islet survival, but its impact on islet cold-ischemic injury remains unexplored. Therefore, the aim of this study was to investigate whether liraglutide can improve islet transplantation efficacy by inhibiting cold-ischemic injury and to explore the underlying mechanisms. METHODS: Liraglutide was applied in a mouse pancreas preservation model and a human islets cold-preservation model, and islet viability, function, oxidative stress levels were evaluated. Furthermore, islet transplantation was performed in a syngeneic mouse model and a human-to-nude mouse islet xenotransplantation model. RESULTS: The supplementation of liraglutide in preservation solution improved islet viability, function, and reduced cell apoptosis. Liraglutide inhibited the oxidative stress of cold-preserved pancreas or islets through upregulating the antioxidant enzyme glutathione levels, inhibiting reactive oxygen species accumulation, and maintaining the mitochondrial membrane integrity, which is associated with the activation of Akt signaling. Furthermore, the addition of liraglutide during cold preservation of donor pancreas or donor islets significantly improved the subsequent transplant outcomes in both syngeneic mouse islet transplantation model and human-to-nude mouse islet xenotransplantation model. CONCLUSIONS: Liraglutide protects islets from cold ischemia-related oxidative stress during preservation and hence improved islet transplantation outcomes, and this protective effect of liraglutide in islets is associated with the activation of Akt signaling.

Recent advances in mesenchymal stem cell therapy for myocardial infarction.

Myocardial infarction refers to the ischemic necrosis of myocardium, characterized by a sharp reduction or interruption of blood flow in the coronary arteries due to the coronary artery occlusion, resulting in severe and prolonged ischemia in the corresponding myocardium and ultimately leading to ischemic necrosis of the myocardium. Given its high risk, it is considered as one of the most serious health threats today. In current clinical practice, multiple approaches have been explored to diminish myocardial oxygen consumption and alleviate symptoms, but notable success remains elusive. Accumulated clinical evidence has showed that the implantation of mesenchymal stem cell for treating myocardial infarction is both effective and safe. Nevertheless, there persists controversy and variability regarding the standardizing MSC transplantation protocols, optimizing dosage, and determining the most effective routes of administration. Addressing these remaining issues will pave the way of integration of MSCs as a feasible mainstream cardiac treatment.

Photoredox-catalyzed carbonylative acylation of styrenes with Hantzsch esters.

Ketones exist widely in naturally occurring products and are indispensable building blocks in organic synthesis. Carbonylation represents one of the most straightforward methods for ketone preparation and has become an attractive field in modern organic chemistry as well. Among the strategies, photocatalytic carbonylation is also worthy of further exploration. Herein, we developed a three-component carbonylation that provides a new method for the synthesis of ketones from Hantzsch esters, CO and styrenes. The reaction was performed under a blue light environment and yields a series of ketones with moderate to good yields.

Iron-Catalyzed Aminoalkylative Carbonylative Cyclization of Alkenes toward α-Tetralones.

Carbonylative multifunctionalization of alkenes is an efficient approach to introduce multiple functional groups into one molecule from easily available materials. Herein, we developed an iron-catalyzed radical relay carbonylative cyclization of alkenes with acetamides. Various α-tetralones can be constructed in moderate yields from readily available substrates with an earth-abundant iron salt as the catalyst.

Theabrownin from Qingzhuan tea prevents high-fat diet-induced MASLD via regulating intestinal microbiota.

The aim of this study was to investigate whether the therapeutic effect of theabrownin extracted from Qingzhuan tea (QTB) on metabolic dysfunction-associated steatosis liver disease (MASLD) is related to the regulation of intestinal microbiota and its metabolite short-chain fatty acids (SCFAs). Mice were divided into four groups and received normal diet (ND), high-fat diet (HFD) and HFD+QTB (180, 360 mg/kg) for 8 weeks. The results showed that QTB significantly reduced the body weight of HFD mice, ameliorated liver lipid and dyslipidemia, and increased the level of intestinal SCFAs in HFD mice. The results of 16 S rRNA showed that the relative abundance of Bacteroides, Blautia and Lachnoclostridium and their main metabolites acetate and propionate were significantly increased after QTB intervention. The relative abundance of Colidextribacter, Faecalibaculum and Lactobacillus was significantly reduced. QTB can also significantly up-regulate the expression of ATGL, PPARα, FFAR2 and FFAR3, and inhibit the expression of LXRα, SREBP-1c, FAS and HMGCR genes. This makes it possible to act as a prebiotic to prevent MASLD.

Lentinus edodes mycelium polysaccharide inhibits AGEs-induced HUVECs pyroptosis by regulating LncRNA MALAT1/miR-199b/mTOR axis and NLRP3/Caspase-1/GSDMD pathway.

A novel Lentinus edodes mycelia polysaccharide (LMP) prepared in our laboratory has been identified to be effective in inhibiting the damage of islet ß cells induced by glucose toxicity. However, whether it can effectively alleviate the pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by advanced glycation end products (AGEs) remains unclear. Bioinformatics and cell biology techniques were used to explore the mechanism of LMP inhibiting AGEs-induced HUVECs damage. The results indicated that AGEs significantly increased the expression of LncRNA MALAT1, decreased cell viability to 79.67 %, increased intracellular ROS level to 248.19 % compared with the control group, which further led to cell membrane rupture. The release of LDH in cellular supernatant was increased to 149.42 %, and the rate of propidium iodide staining positive cells increased to 277.19 %, indicating the cell pyroptosis occurred. However, the above trend was effectively retrieved after the treatment with LMP. LMP effectively decreased the expression of LncRNA MALAT1 and mTOR, promoted the expression of miR-199b, inhibited AGEs-induced HUVECs pyroptosis by regulating the NLRP3/Caspase-1/GSDMD pathway. LncRNA MALAT1 might be a new target for LMP to inhibit AGEs-induced HUVECs pyroptosis. This study manifested the role of LMP in improving diabetes angiopathy and broadens the application of polysaccharide.

Portable robots for upper-limb rehabilitation after stroke: a systematic review and meta-analysis.

BACKGROUND: Robot-assisted upper-limb rehabilitation has been studied for many years, with many randomised controlled trials (RCTs) investigating the effects of robotic-assisted training on affected limbs. The current trend directs towards end-effector devices. However, most studies have focused on the effectiveness of rehabilitation devices, but studies on device sizes are relatively few. GOAL: Systematically review the effect of a portable rehabilitation robot (PRR) on the rehabilitation effectiveness of paralysed upper limbs compared with non-robotic therapy. METHODS: A meta-analysis was conducted on literature that included the Fugl-Meyer Assessment (FMA) obtained from the PubMed and Web of Science (WoS) electronic databases until June 2023. RESULTS: A total of 9 studies, which included RCTs, were completed and a meta-analysis was conducted on 8 of them. The analysis involved 295 patients. The influence on upper-limb function before and after treatment in a clinical environment is analysed by comparing the experimental group using the portable upper-limb rehabilitation robot with the control group using conventional therapy. The result shows that portable robots prove to be effective (FMA: SMD = 0.696, 95% = 0.099 to.293, p < 0.05). DISCUSSION: Both robot-assisted and conventional rehabilitation effects are comparable. In some studies, PRR performs better than conventional rehabilitation, but conventional treatments are still irreplaceable. Smaller size with better portability has its advantages, and portable upper-limb rehabilitation robots are feasible in clinical rehabilitation. CONCLUSION: Although portable upper-limb rehabilitation robots are clinically beneficial, few studies have focused on portability. Further research should focus on modular design so that rehabilitation robots can be decomposed, which benefits remote rehabilitation and household applications.

First Report of Alternaria alternata Causing Leaf Spot on Smooth Bromegrass (Bromus inermis Leyss.) in China.

Smooth bromegrass (Bromus inermis Leyss.) is an important forage crop in northern China. In July 2021, leaf spot symptoms were observed on smooth bromegrass in Ewenki Banner, Hulunbuir, Inner Mongolia. In an area of approximately 0.12 hectares, 95% disease incidence was observed. Ten diseased plants were collected for pathogen isolation. Leaf tissues near the lesions were cut into 5 × 5 mm pieces, surface-disinfested in 75% ethanol for 3 min, and rinsed with sterile distilled water. The pieces were placed on water agar in petri plates and incubated at 25℃ for three days. The resulting colonies were flushed with sterile water and a spore suspension was serially diluted and plated on potato dextrose agar (PDA). A single-spore colony was obtained. Ten isolates were obtained and designated HE1 to HE10. The colony morphology was identical for all isolates, grayish white in color on the upper surface and light black on the underside. The mycelia were light gray and velvety. Conidia were light brown to brown in color and oblate, oblong or oval. The conidial dimensions were typically between 15 to 43 µm by 8 to 9 µm in size. The conidia possessed one to six transverse septa, with slight to distinct constrictions at each division, and zero to two longitudinal septa. These morphological characteristics resembled Alternaria alternata (Fr.) Keissl.. DNA was extracted from three isolates, HE3, HE4 and HE5, using the CTAB method. Polymerase chain reaction (PCR) was performed on the extracted DNA with a set of primers ITS1/ITS4, H31a/H31b, gpd1/gpd2, TEF1-728F/TEF1-986R, and RPB2-5F2/fRPB2-7cR. The amplicon sequences from the three isolates were analyzed using the BLAST in GenBank (https://www.ncbi.nlm.nih.gov/). The results showed a high sequence identity, ranging from 99 to 100%, with the A. alternata strain YTMZ-20-2 across all the genetic markers tested. The strong match reinforced the identification of the strains as A. alternata. The sequences were deposited in GenBank (Table S1). The three fungal isolates were identified as A. alternata based on their morphological and genetic data. To conduct Koch's postulates, the representative isolate HE4 was used. Smooth bromegrass seed was soaked in water for four days and sown in potting soil contained in plastic pots (10 cm diameter × 15 cm height, five seeds/pot) in a greenhouse under a 16-h photoperiod at temperatures between 20 to 25°C and 60% relative humidity. When the plants reached a height of approximately 20 cm, the plants in three pots (replicates) were sprayed with a spore suspension (106 conidial/ml) at 10 ml/pot, and three pots were sprayed with sterile water for control. Five days after inoculation, the plants exhibited leaf spot symptoms similar to those previously described, while the control plants remained unaffected. The causative fungus was successfully re-isolated from the diseased plants and confirmed morphologically and molecularly on its identity as described above. This experiment was independently conducted three times. This is the first report of A. alternata causing leaf spot on smooth bromegrass in China. Since there is risk that the disease could seriously reduce the yield of the forage crop smooth bromegrass, further research is needed.

Sphingomonas lacusdianchii sp. nov., an attached bacterium inhibited by metabolites from its symbiotic cyanobacterium.

An alpha-proteobacterial strain JXJ CY 53 T was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) collected from Lake Dianchi, China. JXJ CY 53 T was observed to be an aerobic, Gram-stain-negative, oval shaped, and mucus-secreting bacterium. It had C18:1ω7c and C16:0 as the major cellular fatty acids, Q-10 as the predominant ubiquinone, and sphingoglycolipid, diphosphatidylglycerol, phosphatidylcholine, and phosphatidylmethylethanolamine as the polar lipids. The G + C content of DNA was 65.85%. The bacterium had 16S rRNA gene sequence identities of 98.9% and 98.7% with Sphingomonas panni DSM 15761 T and Sphingomonas hankookensis KCTC 22579 T, respectively, while less than 97.4% identities with other members of the genus. Further taxonomic analysis indicated that JXJ CY 53 T represented a new member of Sphingomonas, and the species epithet was proposed as Sphingomonas lacusdianchii sp. nov. (type strain JXJ CY 53 T = KCTC 72813 T = CGMCC 1.17657 T). JXJ CY 53 T promoted the growth of MF-905 by providing bio-available phosphorus and nitrogen, plant hormones, vitamins, and carotenoids. It could modulate the relative abundances of nonculturable bacteria associated with MF-905 and influence the interactions of MF-905 and other bacteria isolated from the cyanobacterium, in addition to microcystin production characteristics. Meanwhile, MF-905 could provide JXJ CY 53 T dissolved organic carbon for growth, and control the growth of JXJ CY 53 T by secreting specific chemicals other than microcystins. Overall, these results suggest that the interactions between Microcystis and its attached bacteria are complex and dynamic, and may influence the growth characteristics of the cyanobacterium. This study provided new ideas to understand the interactions between Microcystis and its attached bacteria. KEY POINTS: • A novel bacterium (JXJCY 53 T) was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) • JXJCY 53 T modulated the growth and microcystin production of MF-905 • MF-905 could control the attached bacteria by specific chemicals other than microcystins (MCs).

Identification of an immune-related signature as a prognostic classifier for patients with early-stage head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is the most common type and accounts for 90% of all head and neck cancer cases. Despite advances in early diagnosis and treatment strategies-chemotherapy, surgical resection, and radiotherapy-5-year survival remains grim. For patients with early-stage HNSCC, accurately predicting clinical outcomes is challenging. Considering the pivotal role of the immune system in HNSCC, we developed a reliable immune-related gene signature (IRGS) and explored its predictive accuracy in patients with early-stage HNSCC. Methods: We examined immune gene expression profiles and clinical information from 230 early-stage HNSCC specimens, including 100 cases from The Cancer Genome Atlas (TCGA), 49 cases from the Gene Expression Omnibus (GEO; GSE65858), and 81 cases from an independent clinical cohort. The prognostic signature was constructed using Kaplan-Meier analysis and the least absolute shrinkage and selection operator (LASSO) Cox algorithm. We also explored the IRGS-related biological pathways and immune landscape using bioinformatics analysis. Results: A nine-immune-gene signature was generated to significantly stratify patients into high and low-risk groups. High risk patients exhibited shorter survival time [hazard ratio (HR) =13.795, 95% confidence interval (CI): 3.275-58.109, P<0.001]. The signature demonstrated robust prognostic ability in the training and validation sets and could independently predict overall survival (OS) and relapse-free survival (RFS). Subsequently, the receiver operating characteristic (ROC) curve and C-index confirmed the signature's predictive accuracy compared to clinical parameters. Additionally, cases classified as low risk showed more immune cell infiltration than high-risk cases. Conclusions: Our novel IRGS is a reliable and robust classifier for accurate patient stratification and prognostic evaluation. Future studies will attempt to affirm the signature's clinical application to early-stage HNSCC.

Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections.

Objective: Although glucagon-like peptide 1 (GLP-1) is known to regulate feeding, the central mechanisms contributing to this function remain enigmatic. Here, we aim to test the role of neurons expressing GLP-1 receptors (GLP-1R) in the dorsolateral septum (dLS; dLS GLP-1R ) and their downstream projections on food intake and determine the relationship with feeding regulation. Methods: Using chemogenetic manipulations, we assessed how activation or inhibition of dLS GLP-1R neurons affected food intake in Glp1r-ires-Cre mice. Then, we used channelrhodopsin-assisted circuit mapping, chemogenetics, and electrophysiological recordings to identify and assess the role of the pathway from dLS GLP-1R neurons to the lateral hypothalamic area (LHA) in regulating food intake. Results: Chemogenetic inhibition of dLS GLP-1R neurons increases food intake. LHA is a major downstream target of dLS GLP-1R neurons. The dLS GLP-1R →LHA projections are GABAergic, and chemogenetic inhibition of this pathway also promotes food intake. While chemogenetic activation of dLS GLP-1R →LHA projections modestly decreases food intake, optogenetic stimulation of the dLS GLP-1R →LHA projection terminals in the LHA rapidly suppressed feeding behavior. Finally, we demonstrate that the GLP-1R agonist, Exendin 4 enhances dLS GLP-1R →LHA GABA release. Conclusions: Together, these results demonstrate that dLS-GLP-1R neurons and the inhibitory pathway to LHA can regulate feeding behavior, which might serve as a potential therapeutic target for the treatment of eating disorders or obesity. Highlights: Chemogenetic inhibition of dLS GLP-1R neurons boosts food intake in mice dLS GLP-1R neuron activation does not alter feeding, likely by collateral inhibition dLS GLP-1R neurons project to LHA and release GABA Activation of dLS GLP-1R →LHA axonal terminals suppresses food intake GLP-1R agonism enhances dLS GLP-1R →LHA GABA release via a presynaptic mechanism.

People are an organic unity: Gut-lung axis and pneumonia.

People are an organic unity. Every organ of our body doesn't exist alone. They are a part of our body and have important connections with other tissues or organs. The gut-lung axis is a typical example. Here, we reviewed the current research progress of the gut-lung axis. The main cross-talk between the intestine and lungs was sorted out, i.e. the specific interaction content contained in the gut-lung axis. We determine a relatively clear concept for the gut-lung axis, that is, the gut-lung axis is a cross-talk that the gut and lungs interact with each other through microorganisms and the immune system to achieve bidirectional regulation. The gut and lungs communicate with each other mainly through the immune system and symbiotic microbes, and these two pathways influence each other. The portal vein system and mesenteric lymphatics are the primary communication channels between the intestine and lungs. We also summarized the effects of pneumonia, including Coronavirus disease 2019 (COVID-19) and Community-Acquired Pneumonia (CAP), on intestinal microbes and immune function through the gut-lung axis, and discussed the mechanism of this effect. Finally, we explored the value of intestinal microbes and the gut-lung axis in the treatment of pneumonia through the effect of intestinal microbes on pneumonia.

Integrated management of fruit trees and Bletilla striata: implications for soil nutrient profiles and microbial community structures.

Introduction: Forest medicinal compound systems in agroforestry ecosystems represent a multi-layered cultivation approach that utilizes forest resources efficiently. However, research on how these systems affect soil nutrients and microbial communities is limited. Methods: This study compared the soil chemical properties and microbial communities of Bletilla striata (C) grown alone versus in agroforestry systems with apple (PB), pear (LB), and peach trees (TB), aiming to understand the impact of these systems on soil health and microbial diversity. Results: Soil in the GAB systems showed increased levels of essential nutrients but lower pH and ammonium nitrogen levels compared to the control. Significant improvements in organic matter, total phosphorus, and total potassium were observed in TB, PB, and LB systems, respectively. The bacterial diversity increased in GAB systems, with significant changes in microbial phyla indicative of a healthier soil ecosystem. The correlation between soil properties and bacterial communities was stronger than with fungal communities. Discussion: Integrating B. striata with fruit trees enhances soil nutrients and microbial diversity but may lead to soil acidification. Adjustments such as using controlled-release fertilizers and soil amendments like lime could mitigate negative impacts, improving soil health in GAB systems.

Th2-skewed peripheral T helper cells drives B cells in allergic bronchopulmonary aspergillosis.

INTRODUCTION: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. However, the involvement of T cell subsets remains unclear. METHODS: We enrolled ABPA patients, asthma patients and healthy controls. Th1, Th2, Th17, Treg and IL-21+CD4+T cells in total or sorted subsets of peripheral blood mononuclear cells (PBMCs) and ABPA Bronchoalveolar Lavage fluid (BALF) were analyzed by flow cytometry. RNA sequencing of subsets of CD4+T cells were done in exacerbated ABPA patients and healthy controls. Antibodies of T-B cell co-cultures in vitro were measured. RESULTS: ABPA patients had increased Th2 cells, similar Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T cells was rarely detected in healthy controls but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T cells were mainly peripheral T helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T helper (Tfh) cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B cells into plasmablasts and significantly enhanced the production of IgE. CONCLUSION: We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.