Baicalin suppresses macrophage JNK-mediated adipose tissue inflammation to mitigate insulin resistance in obesity.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix scutellariae (the root of Scutellaria baicalensis Georgi) is a traditional Chinese medicine (TCM) used to treat a wide range of inflammation-related diseases, such as obesity, diabetes, diabetic kidney disease, and COVID-19-associated inflammatory states in the lung and kidney. Baicalin is the major anti-inflammatory component of Radix scutellariae and has shown the potential to inhibit inflammation in metabolic disorders. In this study, we explored the ability and underlying mechanisms of baicalin to modulate the macrophage to mitigate insulin resistance in obesity. MATERIALS AND METHODS: Obese mice were administered baicalin (50 mg/kg/day) intraperitoneally for 3 weeks. RAW264.7 and BMDM cells were stimulated with LPS and treated with baicalin for 24 h, while 3T3-L1 and primary white adipocytes were treated with the supernatants from baicalin-treated RAW264.7 cells for 24 h. RESULTS: The results showed that baicalin significantly improved glucose and insulin tolerance as well as decreased fat and adipose tissue macrophage levels in obese mice. Besides, baicalin significantly reduced serum and adipose tissue IL-1ß, TNF-α and IL-6 levels in obese mice, as well as suppressed LPS-induced IL-1ß, TNF-α and IL-6 expression and release in macrophages. Furthermore, treatment with the supernatant from baicalin-treated RAW264.7 cells increased the levels of PGC-1α, SIRT1, p-IRS-1 and p-AKT in adipocytes. Moreover, baicalin treatment dramatically downregulated macrophage p-p38, p-JNK, and Ac-p65Lys310 levels while increasing SIRT1 both in vivo and in vitro. Importantly, JNK inhibitor SP600125 blocked most of the effects of baicalin on SIRT1, Ac-p65Lys310 and pro-inflammatory factors in macrophages. CONCLUSION: Therefore, these results demonstrated for the first time that baicalin exerts its anti-inflammatory effects in obese adipose tissue macrophages mainly through suppressing JNK/SIRT1/p65 signaling. These findings amplified the mechanisms of baicalin and its potential to attenuate insulin resistance.

Impact of treatment interval between neoadjuvant immunochemotherapy and surgery in lung squamous cell carcinoma.

OBJECTIVE: The optimal timing for surgery following neoadjuvant immunochemotherapy for lung squamous cell carcinoma appears to be a topic of limited data. Many clinical studies lack stringent guidelines regarding this timing. The objective of this study is to explore the effect of the interval between neoadjuvant immunochemotherapy and surgery on survival outcomes in patients with lung squamous cell carcinoma. METHODS: This study conducted a retrospective analysis of patients with lung squamous cell carcinoma who underwent neoadjuvant immunochemotherapy between January 2019 and October 2022 at The First Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups based on the treatment interval: ≤33 days and > 33 days. The primary observational endpoints of the study were Disease-Free Survival (DFS) and Overall Survival (OS). Secondary observational endpoints included Objective response rate (ORR), Major Pathological Response (MPR), and Pathological Complete Remission (pCR). RESULTS: Using the Kaplan-Meier methods, the ≤ 33d group demonstrated a superior DFS curve compared to the > 33d group (p = 0.0015). The median DFS for the two groups was 952 days and 590 days, respectively. There was no statistical difference in the OS curves between the groups (p = 0.66), and the median OS was not reached for either group. The treatment interval did not influence the pathologic response of the tumor or lymph nodes. CONCLUSIONS: The study observed that shorter treatment intervals were associated with improved DFS, without influencing OS, pathologic response, or surgical safety. Patients should avoid having a prolonged treatment interval between neoadjuvant immunochemotherapy and surgery.

A Dual-Gene Reporter-Amplifier Architecture for Enhancing the Sensitivity of Molecular MRI by Water Exchange.

The development of genetic reporters for magnetic resonance imaging (MRI) is essential for investigating biological functions in vivo. However, current MRI reporters have low sensitivity, making it challenging to create significant contrast against the tissue background, especially when only a small fraction of cells express the reporter. To overcome this limitation, we developed an approach for amplifying the sensitivity of molecular MRI by combining a chemogenetic contrast mechanism with a biophysical approach to increase water diffusion through the co-expression of a dual-gene construct comprising an organic anion transporting polypeptide, Oatp1b3, and a water channel, Aqp1. We first show that the expression of Aqp1 amplifies MRI contrast in cultured cells engineered to express Oatp1b3. We demonstrate that the contrast amplification is caused by Aqp1-driven increase in water exchange, which provides the gadolinium ions internalized by Oatp1b3-expressing cells with access to a larger water pool compared with exchange-limited conditions. We further show that our methodology allows cells to be detected using approximately 10-fold lower concentrations of gadolinium than that in the Aqp1-free scenario. Finally, we show that our approach enables the imaging of mixed-cell cultures containing a low fraction of Oatp1b3-labeled cells that are undetectable on the basis of Oatp1b3 expression alone.

A dual-gene reporter-amplifier architecture for enhancing the sensitivity of molecular MRI by water exchange.

The development of genetic reporters for magnetic resonance imaging (MRI) is essential for investigating biological functions in intact animals. However, current MRI reporters have low sensitivity, making it challenging to create significant contrast against the tissue background, especially when only a small percentage of cells express the reporter. To overcome this limitation, we developed an approach that amplifies signals by co-expressing an MRI reporter gene, Oatp1b3, with a water channel, aquaporin-1 (Aqp1). We first show that the expression of Aqp1 amplifies the paramagnetic relaxation effect of Oatp1b3 by facilitating transmembrane water exchange. This mechanism provides Oatp1b3-expressing cells with access to a larger water pool compared with typical exchange-limited conditions. We further demonstrated that our methodology allows dual-labeled cells to be detected using approximately 10-fold lower concentrations of contrast agent than that in the Aqp1-free scenario. Finally, we show that our approach enables the imaging of mixed-cell populations containing a low fraction of Oatp1b3-labeled cells that are otherwise undetectable based on Oatp1b3 expression alone.

Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/mTOR Signaling Pathway.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS: EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.

High-Performance Wearable Organic Photodetectors by Molecular Design and Green Solvent Processing for Pulse Oximetry and Photoplethysmography.

White-light detection from the visible to the near-infrared region is central to many applications such as high-speed cameras, autonomous vehicles, and wearable electronics. While organic photodetectors (OPDs) are being developed for such applications, several challenges must be overcome to produce scalable high-detectivity OPDs. This includes issues associated with low responsivity, narrow absorption range, and environmentally friendly device fabrication. Here, an OPD system processed from 2-methyltetrahydrofuran (2-MeTHF) sets a record in light detectivity, which is also comparable with commercially available silicon-based photodiodes is reported. The newly designed OPD is employed in wearable devices to monitor heart rate and blood oxygen saturation using a flexible OPD-based finger pulse oximeter. In achieving this, a framework for a detailed understanding of the structure-processing-property relationship in these OPDs is also developed. The bulk heterojunction (BHJ) thin films processed from 2-MeTHF are characterized at different length scales with advanced techniques. The BHJ morphology exhibits optimal intermixing and phase separation of donor and acceptor moieties, which facilitates the charge generation and collection process. Benefitting from high charge carrier mobilities and a low shunt leakage current, the newly developed OPD exhibits a specific detectivity of above 1012  Jones over 400-900 nm, which is higher than those of reference devices processed from chlorobenzene and ortho-xylene.

Lectin diversity and their positive roles in WSSV replication through regulation of calreticulin expression and inhibiting ALFs expression.

In biological evolution, gene duplication (GD) generates new genes to facilitate new functions. C-type lectins (CTLs) in crayfish have been extended by GD to expand their family members. In this study, four CTL genes generated by GD were identified from Procambarus clarkii (PcLec1-4). Among these four genes, PcLec1 can also generate new isoforms with different numbers of tandem repeats through DNA slip mispairing. PcLec1-4 was widely expressed in multiple tissues. The expression levels of PcLec1-4 were upregulated in the intestine of P. clarkii upon white spot syndrome virus (WSSV) challenge at multiple time points. Further analysis indicated that GATA transcription factor regulated PcLec1-4 expression. RNA interference and recombinant PcLec1-4 protein injection experiments suggested that PcLec1-4 promoted the expression of calreticulin (PcCRT) and negatively regulated the expression of antimicrobial peptides, thereby promoting WSSV replication. This study contributes to the understanding of the function of CTLs produced by GD during WSSV invasion in crustaceans.

Development of predictive models for assessing the progression and invasiveness of satellite lesions in patients with multiple pulmonary ground glass nodules.

Background: Currently, the appropriate treatment of satellite lesions is still controversial. With this study, we aimed to construct a set of nomograms to determine the characteristics of satellite lesions in patients with multiple pulmonary ground glass nodules (MPGGNs) and propose a reference for the management of satellite lesions. Methods: We retrospectively analyzed patients with MPGGNs who had undergone multiple rounds of surgical resection of primary and satellite lesions, including pathologic examinations after surgical resection. Results: A total of 125 lesions from 105 patients were included in the analysis; 85 lesions were advanced and 40 lesions were not advanced. Among them, 55 invasive pulmonary adenocarcinomas (IPA) and 70 noninvasive pulmonary adenocarcinomas were identified. After the final regression analysis, the patients' age, satellite lesion location, consolidation tumor ratio (CTR), lesion border clarity, and lesion diameter were used to predict satellite lesion progression. Patients' gender, satellite lesion location, lesion diameter, and computed tomography (CT) attenuation values were used to predict the invasiveness of the satellite lesion. The constructed nomograms showed strong discrimination with concordance indices (C indices) of 0.816 and 0.823, respectively. Conclusions: We developed a set of nomograms that can predict the risk of advanced or invasive satellite lesions in patients with MPGGNs. The area under the receiver operating characteristic (ROC) curve (AUC), the C-index, and the calibration curve suggest that the nomogram may be useful in the clinical setting. This model has the potential to help clinicians make treatment recommendations for the remaining lesions while treating the primary lesion in patients with MPGGNs.

Cellular and molecular imaging of CAR-T cell-based immunotherapy.

Chimeric Antigen Receptor T cell (CAR-T) therapy has emerged as a transformative therapeutic strategy for hematological malignancies. However, its efficacy in treating solid tumors remains limited. An in-depth and comprehensive understanding of CAR-T cell signaling pathways and the ability to track CAR-T cell biodistribution and activation in real-time within the tumor microenvironment will be instrumental in designing the next generation of CAR-T cells for solid tumor therapy. This review summarizes the signaling network and the cellular and molecular imaging tools and platforms that are utilized in CAR-T cell-based immune therapies, covering both in vitro and in vivo studies. Firstly, we provide an overview of the existing understanding of the activation and cytotoxic mechanisms of CAR-T cells, compared to the mechanism of T cell receptor (TCR) signaling pathways. We further describe the commonly employed tools for live cell imaging, coupled with recent research progress, with a focus on genetically encoded fluorescent proteins (FPs) and biosensors. We then discuss the utility of diverse in vivo imaging modalities, including fluorescence and bioluminescence imaging, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and photoacoustic (PA) imaging, for noninvasive monitoring of CAR-T cell dynamics within tumor tissues, thereby providing critical insights into therapy's strengths and weaknesses. Lastly, we discuss the current challenges and future directions of CAR-T cell therapy from the imaging perspective. We foresee that a comprehensive and integrative approach to CAR-T cell imaging will enable the development of more effective treatments for solid tumors in the future.

Additive-free molecular acceptor organic solar cells processed from a biorenewable solvent approaching 15% efficiency.

We report on the use of molecular acceptors (MAs) and donor polymers processed with a biomass-derived solvent (2-methyltetrahydrofuran, 2-MeTHF) to facilitate bulk heterojunction (BHJ) organic photovoltaics (OPVs) with power conversion efficiency (PCE) approaching 15%. Our approach makes use of two newly designed donor polymers with an opened ring unit in their structures along with three molecular acceptors (MAs) where the backbone and sidechain were engineered to enhance the processability of BHJ OPVs using 2-MeTHF, as evaluated by an analysis of donor-acceptor (D-A) miscibility and interaction parameters. To understand the differences in the PCE values that ranged from 9-15% as a function of composition, the surface, bulk, and interfacial BHJ morphologies were characterized at different length scales using atomic force microscopy, grazing-incidence wide-angle X-ray scattering, resonant soft X-ray scattering, X-ray photoelectron spectroscopy, and 2D solid-state nuclear magnetic resonance spectroscopy. Our results indicate that the favorable D-A intermixing that occurs in the best performing BHJ film with an average domain size of ∼25 nm, high domain purity, uniform distribution and enhanced local packing interactions - facilitates charge generation and extraction while limiting the trap-assisted recombination process in the device, leading to high effective mobility and good performance.

Cybersecurity in neural interfaces: Survey and future trends.

With the joint advancement in areas such as pervasive neural data sensing, neural computing, neuromodulation and artificial intelligence, neural interface has become a promising technology facilitating both the closed-loop neurorehabilitation for neurologically impaired patients and the intelligent man-machine interactions for general application purposes. However, although neural interface has been widely studied, few previous studies focused on the cybersecurity issues in related applications. In this survey, we systematically investigated possible cybersecurity risks in neural interfaces, together with potential solutions to these problems. Importantly, our survey considers interfacing techniques on both central nervous systems (i.e., brain-computer interfaces) and peripheral nervous systems (i.e., general neural interfaces), covering diverse neural modalities such as electroencephalography, electromyography and more. Moreover, our survey is organized on three different levels: (1) the data level, which mainly focuses on the privacy leakage issue via attacking and analyzing neural database of users; (2) the permission level, which mainly focuses on the prospects and risks to directly use real time neural signals as biometrics for continuous and unobtrusive user identity verification; and (3) the model level, which mainly focuses on adversarial attacks and defenses on both the forward neural decoding models (e.g. via machine learning) and the backward feedback implementation models (e.g. via neuromodulation and stimulation). This is the first study to systematically investigate cybersecurity risks and possible solutions in neural interfaces which covers both central and peripheral nervous systems, and considers multiple different levels to provide a complete picture of this issue.

Integrating Network Pharmacology and Component Analysis to Study the Potential Mechanisms of Qi-Fu-Yin Decoction in Treating Alzheimer's Disease.

Purpose: To elucidate the potential mechanisms of QFY for the treatment of Alzheimer's Disease (AD), and explore the effective substances of QFY. Materials and Methods: UPLC-LTQ-Orbitrap-MS was used to identify the chemical constituents of the serum samples and the cerebrospinal fluid samples of rats after QFY administration. Network pharmacology was used to predict potential targets and pathways of QFY against AD. The AD mice model was established by subcutaneous injection of D-gal for 8 consecutive weeks. New object recognition (NOR) and Morris water maze test (MWM) were used to evaluate the learning and memory abilities of mice. Moreover, the levels of TNF-α, IL-1ß, and IL-18 in the brain hippocampus of mice were determined by ELISA. The expression of Bax, Bcl-2, Caspase-1, PSD95, SYP, ICAM-1 and MCP-1 proteins in the hippocampus was detected by Western blotting. Furthermore, qRT-PCR was used to detect the gene expressions of PSD95, SYP, M1 and M2 polarization markers of microglia, including iNOS, CD16, ARG-1, and IL-10 in the hippocampus. Results: A total of 51 prototype compounds were detected in rat serum and 15 prototype components were identified in rat cerebrospinal fluid. Behavioral experiments revealed that QFY significantly increased the recognition index, decreased the escape latency, increased the platform crossing times and increased the residence time in the target quadrant. QFY also could alleviate the ultrastructural pathological changes in the hippocampus of AD mice. Meanwhile, QFY treatment suppressed the expression of inflammatory factors, such as TNF-α, IL-1ß, and IL-18. QFY improved the synaptic plasticity of the hippocampus in D-gal model mice by significantly increasing the expression of proteins and mRNAs of PSD95 and SYP. Conclusion: QFY could effectively improve the learning and memory impairment of D-gal-induced AD mice by inhibiting the excessive activation of microglia, enhancing the expression of M2 microglia, inhibiting the increase of inflammatory factors, cell adhesion factors and chemokines, anti-apoptosis, and improving synaptic plasticity.

Risk assessment and source apportionment of heavy metals pollution from atmospheric deposition in Nanjing, China.

Heavy metals (HMs) are the toxic pollutants in urban environment, and their sources are complex. Dust might be a good carrier of HMs into ecosystem and human. In this study, 48 dust samples were collected in Nanjing, an industrial city and transportation hub in the Yangtze River Delta, China. The concentrations, spatial distribution, sources and risks of heavy metals (Cr, Ni, Cu, Zn, Cd and Pb) in dust were determined and analyzed. The results showed that although the health risks of some HMs had decreased, Cr, Zn, and Cd had high concentrations and high risks on ecosystem/human. And thus, the total risks of the target HMs were higher than the threshold of non-risks. Especially, children may face the highest possible risks due to the frequent hand-oral ingestion when children play. The hot spot regions of the HMs were mainly in the industrial district in the north, urban, and rural region in south, relating with the industrial, traffic, and agricultural sources, respectively. The analysis for the risks of individual sources further confirmed these sources should be further controlled. The results in this study will provide information on the priority of HMs' monitoring and source management.

Meta-analysis of microbial source tracking for the identification of fecal contamination in aquatic environments based on data-mining.

Microbial source tracking (MST) technology represents an innovative approach employed to trace fecal contamination in environmental water systems. The performance of primers may be affected by amplification techniques, target primer categories, and regional differences. To investigate the influence of these factors on primer recognition performance, a meta-analysis was conducted on the application of MST in water environments using three databases: Web of Science, Scopus, and PubMed (n = 2291). After data screening, 46 studies were included in the final analysis. The investigation encompassed Polymerase Chain Reaction (PCR)/quantitative PCR (qPCR) methodologies, dye-based (SYBR)/probe-based (TaqMan) techniques, and geographical differences of a human host-specific (HF183) primer and other 21 additional primers. The results indicated that the primers analyzed were capable of differentiating host specificity to a certain degree. Nonetheless, by comparing sensitivity and specificity outcomes, it was observed that virus-based primers exhibited superior specificity and recognition capacity, as well as a stronger correlation with human pathogenicity in water environments compared to bacteria-based primers. This finding highlights an important direction for future advancements. Moreover, within the same category, qPCR did not demonstrate significant benefits over conventional PCR amplification methods. In comparing dye-based and probe-based techniques, it was revealed that the probe-based method's advantage lay primarily in specificity, which may be associated with the increased propensity of dye-based methods to produce false positives. Furthermore, the heterogeneity of the HF183 primer was not detected in China, Canada, and Singapore respectively, indicating a low likelihood of regional differences. The variation among the 21 other primers may be attributable to regional differences, sample sources, detection techniques, or alternative factors. Finally, we identified that economic factors, climatic conditions, and geographical distribution significantly influence primer performance.

Team-Based Approach to Reduce Malignancies in People with Diabetes and Obesity.

PURPOSE OF REVIEW: Numerous observations have indicated an increased risk of developing various types of cancers, as well as cancer-related mortality, among patients with diabetes and obesity. The purpose of this review is to outline multiple-cancer screening among these patients through a team-based approach and to present the findings of a pioneering integrated care program designed for patients with obesity with a specific emphasis on cancer prevention. RECENT FINDINGS: A community-based multi-cancer prevention program, which provides all services in one location and utilizes team-based approaches, is reported to be feasible and has the potential to enhance the uptake rate of multiple cancers screening among patients with diabetes and obesity. The team-based approach is a commonly utilized method for managing patients with diabetes, obesity, and cancer, and has been shown to be efficacious. Nevertheless, research on team-based cancer screening programs for patients with diabetes and obesity remains limited. Providing a comprehensive screening for colorectal, prostate, and breast cancer, as well as metabolic syndrome, during a single clinic visit has been proven effective and well-received by participants.

Co-Salient Object Detection With Co-Representation Purification.

Co-salient object detection (Co-SOD) aims at discovering the common objects in a group of relevant images. Mining a co-representation is essential for locating co-salient objects. Unfortunately, the current Co-SOD method does not pay enough attention that the information not related to the co-salient object is included in the co-representation. Such irrelevant information in the co-representation interferes with its locating of co-salient objects. In this paper, we propose a Co-Representation Purification (CoRP) method aiming at searching noise-free co-representation. We search a few pixel-wise embeddings probably belonging to co-salient regions. These embeddings constitute our co-representation and guide our prediction. For obtaining purer co-representation, we use the prediction to iteratively reduce irrelevant embeddings in our co-representation. Experiments on three datasets demonstrate that our CoRP achieves state-of-the-art performances on the benchmark datasets. Our source code is available at https://github.com/ZZY816/CoRP.

Prevalence of ground glass nodules in preschool children: a cross-sectional study.

Background: Following increased screening efforts and the use of thin-slice computed tomography (CT), there has been a considerable increase in the incidence of ground-glass nodules (GGNs) in adults. As a result, we have more and more treatments for ground-glass nodules in adults, but few in children. Most think development pattern of pulmonary GGNs is lung inflammation, tumor, or tuberculosis that are more related to acquired or environmental factors. By studying the incidence of pulmonary GGNs in preschool children, we sought to determine whether we had ground glass nodules in the lung before we were teenagers, but we didn't pay attention to them until later. If the hypothesis holds, we may change the cognition and treatment strategies of ground glass nodules. Even not, there are few epidemiological studies with big data that can fill this gap. Methods: We retrospectively collected the data of all preschool children who had undergone CT at the Children's Hospital of Zhejiang University School of Medicine from 2013 to 2020. These data were filtered according to the following exclusion criteria: severe artifacts, data with identical names to the original data; and patients without follow-up records (≥3 months). Inclusion criteria: must have undergone thin-slice CT (≤1.25 mm) at the first and last follow-up. Two thoracic radiologists with 5 years of experience and another senior one assessed the images. Results: There were a total of 13,361 cases after relevant exclusions, 311 patients were finally enrolled. Clinical features: age at diagnosis (year): 3.56±1.84, female: 147, male: 164, follow-up interval (month): 6.90±4.74, leukemia: 99, pneumonia: 21, lung cyst: 8, space-occupying lesions outside the lungs: 69, foreign body in respiratory tract: 6. After manual screening and reading, only 1 patient meets all requirements. The results showed that between 2013 and 2020, the incidence of GGNs that could be basically determined in the Children's Hospital of Zhejiang University School of Medicine was 0.32%. Conclusions: There have been few previous studies of GGNs in children, and based on our study, we found that there is still some associated morbidity for preschool children, it is rarely found when they are young.

The microbiome of lower respiratory tract and tumor tissue in lung cancer manifested as radiological ground-glass opacity.

Recent studies have confirmed the existence of microbiota in the lungs. The relationship between lung ground-glass opacity (GGO) and microbiota in the lung microenvironment is not clear. In this study, we investigated the microbial composition and diversity in bronchoalveolar lavage fluid (BALF) of diseased lung segments and paired contralateral healthy lung segments from 11 GGO patients. Furthermore, lung GGO and paired normal tissues of 26 GGO patients were explored whether there are microbial characteristics related to GGO. Compared with the control group, the community richness of GGO tissue and BALF of GGO lung segment (α-diversity) and overall microbiome difference (ß-diversity) had no significant difference. The microbiome composition of BALF of GGO segments is distinct from that of paired healthy lung segments [genus (Rothia), order (Lachnospiraceae), family (Lachnospiraceae), genus (Lachnospiraceae_NK4A136_group, Faecalibacterium), and species (Faecalibacterium prausnitzii, Bacteroides uniforms)]. GGO tissue and adjacent lung tissue had more significant differences at the levels of class, order, family, genus, and species level, and most of them are enriched in normal lung tissue. The area under the curve (AUC) using 10 genera-based biomarkers to predict GGO was 91.05% (95% CI: 81.93-100%). In conclusion, this study demonstrates there are significant differences in the lower respiratory tract and lung microbiome between GGO and the non-malignant control group through the BALF and lung tissues. Furthermore, some potential bacterial biomarkers showed good performance to predict GGO.

gem-Halofluorocyclopropanes via [2 + 1] Cycloadditions of In Situ Generated CFX Carbene with Alkenes.

An efficient and operationally simple synthesis of gem-bromofluorocyclopropanes under mild conditions has been developed. The method employs ethyl dibromofluoroacetate (EDBFA) as an accessible and inexpensive source of the bromofluorocarbene (:CFBr) intermediate. The protocol provides the bromofluorocyclopropane products in excellent yields, including examples synthesized in multigram scales. The chlorinated ester, ethyl dichlorofluoroacetate (EDCFA), is also utilized to make the analogous gem-chlorofluorocyclopropanes.

Treatment with spexin mitigates diet-induced hepatic steatosis in vivo and in vitro through activation of galanin receptor 2.

It was reported that spexin as an adipocyte-secreted protein could regulate obesity and insulin resistance. However, the specific metabolic contribution of spexin to fatty liver remains incompletely understood. Herein, we investigated the effects of spexin on hepatosteatosis and explored the underlying molecular mechanisms. HFD-fed mice were injected with spexin and/or GALR2 antagonist M871, while PA-induced HepG2 cells were treated with spexin in the absence or presence of M871 for 12 h, respectively. Gene expression in liver tissues and hepatocytes was assessed by qRT-PCR and western blotting, respectively. The results showed that body weight, visceral fat content, liver lipid droplet formation, hepatic intracellular triglyceride, and serum triglyceride were reduced in spexin-treated mice. Furthermore, spexin increased the expression of hepatic CPT1A, PPARα, SIRT1, KLF9, PGC-1α and PEPCK in vivo and in vitro. Additionally, spexin treatment improved glucose tolerance and insulin sensitivity in mice fed the HFD. Interestingly, these spexin-mediated beneficial effects were abolished by the GALR2 antagonist M871 in mice fed HFD and PA-induced HepG2 cells, suggesting that spexin mitigated HFD-induced hepatic steatosis by activating the GALR2, thereby increasing CPT1A, PPARα, SIRT1, KLF9, PGC-1α and PEPCK expression. Taken together, these data suggest that spexin ameliorates NAFLD by improving lipolysis and fatty acid oxidation via activation of GALR2 signaling.