Effects of selenoprotein extracts from Cardamine hupingshanensis on growth, selenium metabolism, antioxidant capacity, immunity and intestinal health in largemouth bass Micropterus salmoides.

This study aimed to assess the impact of dietary selenoprotein extracts from Cardamine hupingshanensis (SePCH) on the growth, hematological parameters, selenium metabolism, immune responses, antioxidant capacities, inflammatory reactions and intestinal barrier functions in juvenile largemouth bass (Micropterus salmoides). The base diet was supplemented with four different concentrations of SePCH: 0.00, 0.30, 0.60 and 1.20 g/Kg (actual selenium contents: 0.37, 0.59, 0.84 and 1.30 mg/kg). These concentrations were used to formulate four isonitrogenous and isoenergetic diets for juvenile largemouth bass during a 60-day culture period. Adequate dietary SePCH (0.60 and 1.20 g/Kg) significantly increased weight gain and daily growth rate compared to the control groups (0.00 g/Kg). Furthermore, 0.60 and 1.20 g/Kg SePCH significantly enhanced amounts of white blood cells, red blood cells, platelets, lymphocytes and monocytes, and levels of hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin in the hemocytes. In addition, 0.60 and 1.20 g/Kg SePCH increased the mRNA expression levels of selenocysteine lyase, selenophosphate synthase 1, 15 kDa selenoprotein, selenoprotein T2, selenoprotein H, selenoprotein P and selenoprotein K in the fish liver and intestine compared to the controls. Adequate SePCH not only significantly elevated the activities of antioxidant enzymes (Total superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase), the levels of total antioxidant capacity and glutathione, while increased mRNA transcription levels of NF-E2-related factor 2, Cu/Zn-superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase. However, adequate SePCH significantly decreased levels of malondialdehyde and H2O2 and the mRNA expression levels of kelch-like ECH-associated protein 1a and kelch-like ECH-associated protein 1b in the fish liver and intestine compared to the controls. Meanwhile, adequate SePCH markedly enhanced the levels of immune factors (alkaline phosphatase, acid phosphatase, lysozyme, complement component 3, complement component 4 and immunoglobulin M) and innate immune-related genes (lysozyme, hepcidin, liver-expressed antimicrobial peptide 2, complement component 3 and complement component 4) in the fish liver and intestine compared to the controls. Adequate SePCH reduced the levels of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin 8, interleukin 1ß and interferon γ), while increasing transforming growth factor ß1 levels at both transcriptional and protein levels in the liver and intestine. The mRNA expression levels of mitogen-activated protein kinase 13 (MAPK 13), MAPK14 and nuclear factor kappa B p65 were significantly reduced in the liver and intestine of fish fed with 0.60 and 1.20 g/Kg SePCH compared to the controls. Histological sections also demonstrated that 0.60 and 1.20 g/Kg SePCH significantly increased intestinal villus height and villus width compared to the controls. Furthermore, the mRNA expression levels of tight junction proteins (zonula occludens-1, zonula occludens-3, Claudin-1, Claudin-3, Claudin-5, Claudin-11, Claudin-23 and Claudin-34) and Mucin-17 were significantly upregulated in the intestinal epithelial cells of 0.60 and 1.20 g/Kg SePCH groups compared to the controls. In conclusion, these results found that 0.60 and 1.20 g/Kg dietary SePCH can not only improve growth, hematological parameters, selenium metabolism, antioxidant capacities, enhance immune responses and intestinal functions, but also alleviate inflammatory responses. This information can serve as a useful reference for formulating feeds for largemouth bass.

Ventilation failure after endotracheal intubation in an infant with abdominal compartment syndrome: A case report.

Intra-abdominal hypertension and abdominal compartment syndrome (ACS) are distinct clinical stages of pathology caused by increased intra-abdominal pressure, which may lead to respiratory and circulatory dysfunction in children and is associated with high pediatric mortality. An emergency exploratory laparotomy was planned for an infant with ACS. After induction of anesthesia and endotracheal intubation, the patient developed ventilation failure and any management was ineffective. Ventilation was resumed after a race against time abdominal decompression by the surgical team. Abdominal decompression is the primary treatment to relieve respiratory and circulatory failure in children with ACS.

Arabinose Plays an Important Role in Regulating the Growth and Sporulation of Bacillus subtilis NCD-2.

A microbial fungicide developed from Bacillus subtilis NCD-2 has been registered for suppressing verticillium wilt in crops in China. Spores are the main ingredient of this fungicide and play a crucial role in suppressing plant disease. Therefore, increasing the number of spores of strain NCD-2 during fermentation is important for reducing the cost of the fungicide. In this study, five kinds of carbon sources were found to promote the metabolism of strain NCD-2 revealed via Biolog Phenotype MicroArray (PM) technology. L-arabinose showed the strongest ability to promote the growth and sporulation of strain NCD-2. L-arabinose increased the bacterial concentration and the sporulation efficiency of strain NCD-2 by 2.04 times and 1.99 times compared with D-glucose, respectively. Moreover, L-arabinose significantly decreased the autolysis of strain NCD-2. Genes associated with arabinose metabolism, sporulation, spore resistance to heat, and spore coat formation were significantly up-regulated, and genes associated with sporulation-delaying protein were significantly down-regulated under L-arabinose treatment. The deletion of msmX, which is involved in arabinose transport in the Bacillus genus, decreased growth and sporulation by 53.71% and 86.46% compared with wild-type strain NCD-2, respectively. Complementing the mutant strain by importing an intact msmX gene restored the strain's growth and sporulation.

Identification and Expressional Analysis of Putative PRDI-BF1 and RIZ Homology Domain-Containing Transcription Factors in Mulinia lateralis.

Mollusca represents one of the ancient bilaterian groups with high morphological diversity, while the formation mechanisms of the precursors of all germ cells, primordial germ cells (PGCs), have not yet been clarified in mollusks. PRDI-BF1 and RIZ homology domain-containing proteins (PRDMs) are a group of transcriptional repressors, and PRDM1 (also known as BLIMP1) and PRDM14 have been reported to be essential for the formation of PGCs. In the present study, we performed a genome-wide retrieval in Mulinia lateralis and identified 11 putative PRDMs, all of which possessed an N-terminal PR domain. Expressional profiles revealed that all these prdm genes showed specifically high expression levels in the given stages, implying that all PRDMs played important roles during early development stages. Specifically, Ml-prdm1 was highly expressed at the gastrula stage, the key period when PGCs arise, and was specifically localized in the cytoplasm of two or three cells of blastula, gastrula, or trochophore larvae, matching the typical characteristics of PGCs. These results suggested that Ml-prdm1-positive cells may be PGCs and that Ml-prdm1 could be a candidate marker for tracing the formation of PGCs in M. lateralis. In addition, the expression profiles of Ml-prdm14 hinted that it may not be associated with PGCs of M. lateralis. The present study provides insights into the evolution of the PRDM family in mollusks and offers a better understanding of the formation of PGCs in mollusks.

Non-Destructive Detection of the Freshness of Air-Modified Mutton Based on Near-Infrared Spectroscopy.

Monitoring and identifying the freshness levels of meat holds significant importance in the field of food safety as it directly relates to human dietary safety. Traditional packaging methods for lamb meat quality assessment present issues such as cumbersome operations and irreversible damage. This research proposes a quality assessment method for modified atmosphere packaging lamb meat using near-infrared spectroscopy and multi-parameter fusion. Fresh lamb meat quality is taken as the research subject, comparing various physicochemical indicators and near-infrared spectroscopic information under different temperatures (4 °C and 10 °C) and different modified atmosphere packaging combinations. Through precision parameter comparison, rebound and TVB-N values are selected as the modeling parameters. Six spectral preprocessing methods (multi-scatter calibration, MSC; standard normal variate transformation, SNV; normalization; Savitzky-Golay smoothing, SG; Savitzky-Golay 1 derivative, SG-1st; and Savitzky-Golay 2 derivative, SG-2nd), and three feature wavelength selection methods (competitive adaptive reweighted sampling, CARS; successive projections algorithm, SPA; and uninformative variable elimination, UVE) are compared. Partial least squares (PLS) and support vector machine (SVM) are used to construct prediction models for chilled fresh lamb meat quality. The results show that when rebound is used as a parameter, the SG-2nd-SPA-PLSR model has the highest accuracy, with a determination coefficient R2p of 0.94 for the prediction set. When TVB-N is used as a parameter, the MSC-UVE-SVM model has the highest accuracy, with an R2p of 0.95 for the prediction set. In conclusion, the use of near-infrared spectroscopic analysis enables rapid and non-destructive prediction and evaluation of lamb meat freshness, including its textural characteristics and TVB-N content under different modified atmosphere packaging. This study provides a theoretical basis and technical support for further encapsulating the models into portable devices and developing portable near-infrared spectrometers to rapidly determine lamb meat freshness.

Evaluation of postoperative recovery: past, present and future.

Postoperative recovery, as a window to observe perioperative treatment effect and patient prognosis, is a common outcome indicator in clinical research and has attracted more and more attention of surgeons and anaesthesiologists. Postoperative recovery is a subjective, multidimensional, long-term, complex process, so it is unreasonable to only use objective indicators to explain it. Currently, with the widespread use of patient-reported outcomes, various scales become the primary tools for assessing postoperative recovery. Through systematic search, we found 14 universal recovery scales, which have different structures, contents and measurement properties, as well as their own strengths and weaknesses. We also found that it is urgently necessary to perform further researches and develop a scale that can serve as the gold universal standard to evaluate postoperative recovery. In addition, with the rapid development of intelligent equipment, the establishment and validation of electronic scales is also an interesting direction.

Combined effect of simulated microgravity and low-dose ionizing radiation on structure and antibiotic resistance of a synthetic community model of bacteria isolated from spacecraft assembly room.

Understanding the structural and antibiotic resistance changes of microbial communities in space environments is critical for identifying potential pathogens that may pose health risks to astronauts and for preventing and controlling microbial contamination. The research to date on microbes under simulated space factors has primarily been carried out on single bacterial species under the individual effects of microgravity or low-dose radiation. However, microgravity (MG) and low-dose ionizing radiation (LDIR) coexist in the actual spacecraft environment, and microorganisms coexist as communities in the spacecraft environment. Thus, the microbial response to the real changes present during space habitation has not been adequately explored. To address this knowledge gap, we compared the dynamics of community composition and antibiotic resistance of synthetic bacterial communities under simulated microgravit, low-dose ionizing radiation, and the conditions combined, as it occurs in spacecraft. To ensure representative bacteria were selected, we co-cultured of 12 bacterial strains isolated from spacecraft cleanrooms. We found that the weakened competition between communities increased the possibility of species coexistence, community diversity, and homogeneity. The number of Bacilli increased significantly, while different species under the combined conditions showed various changes in abundance compared to those under the individual conditions. The resistance of the synthetic community to penicillins increased significantly under low doses of ionizing radiation but did not change significantly under simulated microgravity or the combined conditions. The results of functional predictions revealed that antibiotic biosynthesis and resistance increased dramatically in the community under space environmental stress, which confirmed the results of the drug sensitivity assays. Our results show that combined space environmental factors exert different effects on the microbial community structure and antibiotic resistance, which provides new insights into our understanding of the mechanisms of evolution of microorganisms in spacecraft, and is relevant to effective microbial pollution prevention and control strategies.

Prediction errors arising from switches between major and minor modes in music: An fMRI study.

The major and minor modes in Western music have positive and negative connotations, respectively. The present fMRI study examined listeners' neural responses to switches between major and minor modes. We manipulated the final chords of J. S. Bach's keyboard pieces so that each major-mode passage ended with either the major (Major-Major) or minor (Major-Minor) tonic chord, and each minor-mode passage ended with either the minor (Minor-Minor) or major (Minor-Major) tonic chord. If the final major and minor chords have positive and negative reward values respectively, the Major-Minor and Minor-Major stimuli would cause negative and positive reward prediction errors (RPEs) respectively in a listener's brain. We found that activity in a frontoparietal network was significantly higher for Major-Minor than for Major-Major. Based on previous research, these results support the idea that a major-to-minor switch causes negative RPE. The contrast of Minor-Major minus Minor-Minor yielded activation in the ventral insula and visual cortex, speaking against the idea that a minor-to-major switch causes positive RPE. We discuss our results in relation to executive functions and the emotional connotations of major versus minor modes.

Comparative analysis of the efficacy and safety of electromagnetic navigation bronchoscopy combined with x-ray or radial endobronchial ultrasound biopsy in the diagnosis of small peripheral pulmonary nodules.

OBJECTIVE: To compare the clinical value and safety of electromagnetic navigation bronchoscopy (ENB) combined with radial endobronchial ultrasound (R-EBUS) or x-ray in the diagnosis of small peripheral pulmonary nodules that cannot be diagnosed by conventional bronchoscopy. METHODS: Fifty-six patients with peripheral pulmonary nodules of <3 cm in diameter who underwent bronchoscopy at the First Affiliated Hospital of Soochow University and Dushu Lake Hospital of Soochow University from February 2019 to January 2022 were selected as the study subjects, including 24 patients who underwent ENB combined with x-ray and 32 patients who underwent ENB combined with R-EBUS. ENB was used as the guiding method in both groups, and x-ray group and R-EBUS group were combined with x-ray and R-EBUS, respectively, to determine whether the lesion was reached. In x-ray group, biopsy and brushing were performed under fluoroscopic guidance. Using the results of surgery, puncture pathology, or clinical follow-up 1 year as the gold standard, the diagnostic sensitivity, specificity, negative predictive value (NPV), diagnostic yield, negative likelihood ratio (LR-), Youden index, missed diagnosis rate, success rate, and κ value were compared between the two groups, and the occurrence of postoperative complications was also compared between the two groups. RESULTS: The negative predictive value of the R-EBUS group was significantly better than that of the x-ray group (p = 0.006). CONCLUSION: Even with smaller nodule diameters, the negative predictive value of ENB combined with R-EBUS were still higher than that of the x-ray group.

Novel flexible sensing technology for nondestructive detection on live fish health/quality during waterless and low-temperature transportation.

Fish health/quality issues are increasingly attracting attention during waterless and low-temperature transportation. Nondestructive detection has become a great need for an effective method to improve fish health/quality. Currently, emerging Internet of Things, novel flexible electronics and data fusion technology have received great interest for nondestructive detection on live fish health/quality. This paper analysized nondestructive detection mechanisms using novel flexible sensing technology to achieve high-precision sensing of key parameters, and machine learning based data fusion modeling to achieve live fish health/quality nondestructive evaluation during waterless and low-temperature transportation. Recent studies on novel flexible electrochemical and physiological biosensors development and application for solving key ambient and physiological parameter sensing were summarized. The ML based data fusion modeling framework and application for live fish health/quality nondestructive evaluation was also highlighted. The future perspective is also proposed to provide promising solutions for accurate sensing of multi-parameter and real applications of live fish health/quality nondestructive detection during waterless and low-temperature transportation.

The Bioavailability of Glycyrrhizinic Acid Was Enhanced by Probiotic Lactobacillus rhamnosus R0011 Supplementation in Liver Fibrosis Rats.

Glycyrrhizinic acid (GL) is clinically applied to treat liver injury, and the bioavailability of orally administered GL is closely related to the gut microbiota. Therefore, the dysbiosis of gut flora in liver injury could significantly influence GL bioavailability. Still, less is known about the impact of probiotic supplementation on the bio-absorption process of oral medication, especially under a pathological state. Herein, probiotic L. rhamnosus R0011 (R0011) with a high viability in the harsh gastrointestinal environment was selected, and the effect of R0011 on the GL bioavailability in rats was investigated. Four groups of rats (n = 6 per group) were included: the normal group (N group), the normal group supplemented with R0011 (NLGG group), CCl4-induced chronic liver injury model (M group), and the model group supplemented with R0011 (MLGG group). Our results showed that liver injury was successfully induced in the M and MLGG groups via an intraperitoneal injection of 50% (v/v) CCl4 solution. Healthy rats supplemented with R0011 could increase the bioavailability of GL by 1.4-fold compared with the normal group by plasma pharmacokinetic analysis. Moreover, the GL bioavailability of MLGG group was significantly increased by 4.5-fold compared with the model group. R0011 directly improved gut microbial glucuronidase and downregulated the host intestinal drug transporter gene expression of multidrug resistance protein 2 (MRP2). More critically, R0011 restored the gut microbiota composition and regulated the metabolic function, significantly enhancing the microbial tryptophan metabolic pathway compared with the pathological state, which may indirectly promote the bioavailability of GL. Overall, these data may provide possible strategies by which to address the low bioavailability of traditional medicine through probiotic intervention.

Single-nucleus RNA sequencing reveals the shared mechanisms inducing cognitive impairment between COVID-19 and Alzheimer's disease.

Alzheimer's disease (AD)-like cognitive impairment, a kind of Neuro-COVID syndrome, is a reported complication of SARS-CoV-2 infection. However, the specific mechanisms remain largely unknown. Here, we integrated single-nucleus RNA-sequencing data to explore the potential shared genes and pathways that may lead to cognitive dysfunction in AD and COVID-19. We also constructed ingenuity AD-high-risk scores based on AD-high-risk genes from transcriptomic, proteomic, and Genome-Wide Association Studies (GWAS) data to identify disease-associated cell subtypes and potential targets in COVID-19 patients. We demonstrated that the primary disturbed cell populations were astrocytes and neurons between the above two dis-eases that exhibit cognitive impairment. We identified significant relationships between COVID-19 and AD involving synaptic dysfunction, neuronal damage, and neuroinflammation. Our findings may provide new insight for future studies to identify novel targets for preventive and therapeutic interventions in COVID-19 patients.

Unbiased transcriptome mapping and modeling identify candidate genes and compounds of osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage loss, subchondral bone remodeling, and synovial inflammation. Given that the current therapies for advanced OA patients are limited, the understanding of mechanisms and novel therapies are urgently needed. In this study, we employed the weighted gene co-expression network (WGCNA) method and the connectivity map (CMap) database to identify the candidate target genes and potential compounds. Four groups of co-expressing genes were identified as the OA-related modules. The biological annotations of these modules indicated some critical hallmarks of OA and aging, such as mitochondrial dysfunctions and abnormal energy metabolism, and the signaling pathways, such as MAPK, TNF, and PI3K/Akt signaling pathways. Some genes, such as RELA and GADD45B, were predicted to extensively involve these critical pathways, indicating their potential functions in OA mechanisms. Moreover, we constructed the co-expressing networks of modules and identified the hub genes based on network topology. GADD45B, MAFF, and MYC were identified and validated as the hub genes. Finally, anisomycin and MG-262 were predicted to target these OA-related modules, which may be the potential drugs for OA therapy. In conclusion, this study identified the significant modules, signaling pathways, and hub genes relevant to OA and highlighted the potential clinical value of anisomycin and MG-262 as novel therapies in OA management.

Salvage therapy of osimertinib plus anlotinib in advanced lung adenocarcinoma with leptomeningeal metastasis: A case report.

Leptomeningeal metastasis (LM) is one of the most serious complications of advanced non-small cell lung cancer (NSCLC) and lacks standard treatment. Patients with LM often have a poor prognosis. Here, we report a 51-year-old man diagnosed as advanced lung adenocarcinoma and gene sequencing indicated no sensitive driver gene mutation. Pemetrexed and cisplatin plus bevacizumab was administered as first-line therapy. He received pembrolizumab plus nab-paclitaxel as second-line therapy and developed neurological symptoms soon. Later, he was diagnosed LM by cerebrospinal fluid (CSF) cytology and gene sequencing of lung tissue rebiopsy demonstrated epidermal growth factor receptor (EGFR) sensitive mutation. The patient received high-dose (160mg) osimertinib therapy but still could not tolerate severe neurological symptoms and developed cardiac adverse event. After that, standard-dose (80mg) osimertinib plus anlotinib was administered and this treatment regimen resulted in the alleviation of neurological symptoms. As the recent follow up, the curative effect was evaluated stable disease (SD) and the patient gained a progression-free survival (PFS) of more than 15 months. We report this successful salvage therapy of osimertinib plus anlotinib in an advanced lung adenocarcinoma patient who developed LM after failure on previous treatment until EGFR mutation was confirmed through rebiopsy.

Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm.

Identifying biomarkers for abdominal aortic aneurysms (AAA) is key to understanding their pathogenesis, developing novel targeted therapeutics, and possibly improving patients outcomes and risk of rupture. Here, we identified AAA biomarkers from public databases using single-cell RNA-sequencing, weighted co-expression network (WGCNA), and differential expression analyses. Additionally, we used the multiple machine learning methods to identify biomarkers that differentiated large AAA from small AAA. Biomarkers were validated using GEO datasets. CIBERSORT was used to assess immune cell infiltration into AAA tissues and investigate the relationship between biomarkers and infiltrating immune cells. Therefore, 288 differentially expressed genes (DEGs) were screened for AAA and normal samples. The identified DEGs were mostly related to inflammatory responses, lipids, and atherosclerosis. For the large and small AAA samples, 17 DEGs, mostly related to necroptosis, were screened. As biomarkers for AAA, G0/G1 switch 2 (G0S2) (Area under the curve [AUC] = 0.861, 0.875, and 0.911, in GSE57691, GSE47472, and GSE7284, respectively) and for large AAA, heparinase (HPSE) (AUC = 0.669 and 0.754, in GSE57691 and GSE98278, respectively) were identified and further verified by qRT-PCR. Immune cell infiltration analysis revealed that the AAA process may be mediated by T follicular helper (Tfh) cells and the large AAA process may also be mediated by Tfh cells, M1, and M2 macrophages. Additionally, G0S2 expression was associated with neutrophils, activated and resting mast cells, M0 and M1 macrophages, regulatory T cells (Tregs), resting dendritic cells, and resting CD4 memory T cells. Moreover, HPSE expression was associated with M0 and M1 macrophages, activated and resting mast cells, Tregs, and resting CD4 memory T cells. Additional, G0S2 may be an effective diagnostic biomarker for AAA, whereas HPSE may be used to confer risk of rupture in large AAAs. Immune cells play a role in the onset and progression of AAA, which may improve its diagnosis and treatment.

iTRAQ-based proteomic analysis of Bacillus subtilis strain NCD-2 regulated by PhoPR two-component system: A comparative analysis with transcriptomics revealed the regulation for fengycin production by branched chain amino acids.

The PhoPR two-component system (TCS) is a signal transduction pathway to regulate the phosphate starvation response in Bacillus subtilis and regulated fengycin production in strain NCD-2 under low phosphate condition. The purpose of this study was to characterize the proteome level responses in the phoP-null mutant (MP) and the phoR-null mutant (MR), and to integrate the proteomics with the transcriptomic data obtained previously. The metabolic pathway for fengycin was predicted based on omics analysis as well as molecular genetics assay. Results showed the proteins and genes associated with biosynthesis of branched chain amino acids (BCAAs) were regulated by PhoPR TCS, and liquid chromatography mass spectrometry (LC-MS) analysis also confirmed that the production of BCAAs was down-regulated in the MP and MR mutants, when compared to wild-type strain NCD-2. Protein network analysis showed that the BCAA metabolism was linked to the biosynthesis of lipopeptides. The MP and MR strains decreased the fengycin production when cultured in modified Landy medium supplied with 0.42 mM phosphate, however, the fengycin production could be restored when the glutamic acid was replaced with BCAAs that were added to modified Landy medium. The lpdV gene, which is responsible for the BCAA degradation process, was deleted in strain NCD-2. Compared with the wild-type strain, the lpdV mutant produced significantly less fengycin in the medium supplied with BCAAs. Considered together, the results of this study indicate that the PhoPR TCS regulates fengycin production by affecting BCAA biosynthesis.

A retrospective cohort study of sintilimab and pembrolizumab as first-line treatments for advanced non-small cell lung cancer.

Background: Pembrolizumab and sintilimab have both been approved by the China National Medical Products Administration (NMPA) for the first-line treatment of advanced non-small cell lung cancer (NSCLC). These two drugs have several differences in biological characteristics and population in clinical trials. The current retrospective study was conducted to compare the efficacy and safety of sintilimab and pembrolizumab as first-line treatments in patients with advanced NSCLC. Methods: Consecutive patients with advanced NSCLC who received sintilimab or pembrolizumab as first-line therapy, with or without chemotherapy, from November 2018 to October 2021 in the First Affiliated Hospital of Soochow University and Dushu Lake Hospital Affiliated to Soochow University were retrospectively reviewed. Clinical data and treatment response were collected and survival was followed up. Kaplan-Meier method was used to estimate survival curves. The patients were divided into the sintilimab group and the pembrolizumab group according to the PD-1 inhibitors they received during treatment. The primary objective was to compare objective response rate (ORR) and progression-free survival (PFS) between the two groups. The secondary objectives were to compare disease control rate (DCR) and analyze adverse events (AEs) of the two groups. Results: A total of 124 patients were enrolled, including 68 patients (54.8%) in the sintilimab group and 56 patients (45.2%) in the pembrolizumab group. The baseline characteristics of the patients were comparable between the two groups. The ORR was 50% in the sintilimab group and 46.4% in the pembrolizumab group (P=0.69). The DCR was 89.7% and 89.3% in the sintilimab group and the pembrolizumab group, respectively (P=0.94). The median PFS time was 9.9 months in patients treated with sintilimab compared to 10.8 months in patients on pembrolizumab treatment [hazard ratio (HR) =0.960; 95% confidence interval (CI): 0.574-1.606; P=0.875]. The median OS time was not reached in either group of patients. The incidence of grade 3-4 treatment-related adverse events (TRAEs) was 25% (17/68) in the sintilimab group and 21.4% (12/56) in the pembrolizumab group. Conclusions: Sintilimab has similar efficacy to pembrolizumab as a first-line treatment option for patients with advanced NSCLC in clinical practice, with manageable AEs.

Berberine and its derivatives represent as the promising therapeutic agents for inflammatory disorders.

Berberine, with the skeleton of quaternary ammonium, has been considered as the well-defined natural product in treating multiple diseases, including inflammation, acute and chronic infection, autoimmune diseases, and diabetes. However, due to the low bioavailability and systemic exposure, broad clinical applications of berberine have been largely impeded. Numerous studies have been conducted to further explore the therapeutic capacities of berberine in preclinical and clinical trials. Over the past, berberine and its derivatives have been shown to possess numerous pharmacological activities, as evidenced in intestinal, pulmonary, skin, and bone inflammatory disorders. In the present review, the pharmacological impact of berberine on inflammatory diseases are fully discussed, with indication that berberine and its potential derivatives represent promising natural therapeutic agents with anti-inflammatory properties.

Fatty acid export protein BnFAX6 functions in lipid synthesis and axillary bud growth in Brassica napus.

Sugar is considered as the primary regulator of plant apical dominance, whereby the outgrowth of axillary buds is inhibited by the shoot tip. However, there are some deficiencies in this theory. Here, we reveal that Fatty Acid Export 6 (BnFAX6) functions in FA transport, and linoleic acid or its derivatives acts as a signaling molecule in regulating apical dominance of Brassica napus. BnFAX6 is responsible for mediating FA export from plastids. Overexpression of BnFAX6 in B. napus heightened the expression of genes involved in glycolysis and lipid biosynthesis, promoting the flow of photosynthetic products to the biosynthesis of FAs (including linoleic acid and its derivatives). Enhancing expression of BnFAX6 increased oil content in seeds and leaves and resulted in semi-dwarf and increased branching phenotypes with more siliques, contributing to increased yield per plant relative to wild-type. Furthermore, decapitation led to the rapid flow of the carbon from photosynthetic products to FA biosynthesis in axillary buds, consistent with the overexpression of BnFAX6 in B. napus. In addition, free FAs, especially linoleic acid, were rapidly transported from leaves to axillary buds. Increasing linoleic acid in axillary buds repressed expression of a key transcriptional regulator responsible for maintaining bud dormancy, resulting in bud outgrowth. Taken together, we uncovered that BnFAX6 mediating FA export from plastids functions in lipid biosynthesis and in axillary bud dormancy release, possibly through enhancing linoleic acid level in axillary buds of B. napus.