Lonicerae Japonicae Flos refers to the dried flower buds or flowers about to open of Lonicera japonica （Caprifoliaceae）. Its dried flower buds or early blooming flowers are listed in the Pharmacopoeia of the People's Republic of China （2020 edition） as official medicinal materials. As a Chinese medicine with "heat-clearing and detoxifying" properties and a classic medicinal-edible resource， it is mainly produced in northern authentic producing regions such as Shandong， Henan， and Hebei in China. Lonicerae Japonicae Flos contains abundant bioactive substances that are considered safe and effective， with functions including relieving sore throat， antibacterial and anti-inflammatory effects， and immune regulation. In recent years， with the modernization of traditional Chinese medicine （TCM） and the rapid development of the "big health" industry， Lonicerae Japonicae Flos has become a research hotspot in the fields of natural medicines and functional foods due to its multi-target pharmacological activities and broad application potential. To date， chemical constituents identified from Lonicerae Japonicae Flos include organic acids， flavonoids， iridoids， triterpenes， triterpenoid saponins， and volatile oils. Modern pharmacological studies have shown that Lonicerae Japonicae Flos possesses anti-inflammatory， antibacterial， antioxidant， antiviral， antidiabetic， cardiovascular and neuroprotective， and immunomodulatory activities. In terms of modern applications， Lonicerae Japonicae Flos has developed into a full industrial chain covering pharmaceuticals， health products， daily chemical products， and food additives， demonstrating high medicinal and health value. Strengthening the development of Lonicerae Japonicae Flos-based health products is of great significance. Based on relevant domestic and international literature， this paper systematically reviews the innovative applications of Lonicerae Japonicae Flos in traditional medicine， modern clinical formulations， health foods， and daily chemical products from the perspectives of chemical composition， pharmacological effects， and modern applications， aiming to further deepen basic research on Lonicerae Japonicae Flos. Meanwhile， this paper analyzes and proposes suggestions for promoting applied research on Lonicerae Japonicae Flos， in order to provide a scientific basis for its sound development and to offer references for the rational development and comprehensive utilization of medicinal and edible resources.

Objective:To investigate the therapeutic efficacy and disruptive effects of Meropenem（MEM）-loaded microbubbles（MBs）combined with ultrasound targeted microbubble destruction（UTMD）technology on Escherichia coli and its biofilm.Methods:MEM-MBs were prepared using the thin-film hydration method，and their characterization was assessed using a Zeta potential analyzer，with morphological observations conducted under an optical microscope. An in vitro biofilm model of periprosthetic joint infection（PJI）caused by Escherichia coli was constructed，and the morphology of the biofilm and the distribution of MEM-MBs in the bacterial biofilm were observed under a laser confocal microscope after staining the biofilm with SYTO59 staining and DIL staining for Microbubbles. The biofilm morphology and the distribution of MEM-MBs in bacterial biofilm were observed under laser confocal microscope. The biofilms were randomly divided into 5 groups using a random number table：control，Meropenem（MEM），MEM-MBs，UTMD，and MEM-MBs+UTMD，with 12 samples per group. After applying the respective interventions，scanning electron microscopy（SEM）and laser scanning confocal microscopy（LSCM）were employed to observe the effects on the morphology and structure of Escherichia coli and its biofilm. Crystal violet staining was utilized to determine and compare the biofilm density among groups using a microplate reader. LSCM was also used to observe the biofilm thickness，while both LSCM and spread plate counting were employed to assess bacterial viability differences across groups.Results:①MEM-MBs meeting the experimental requirements were successfully constructed.②A dense Escherichia coli biofilm visible under both the naked eye and LSCM was established，with a thickness of（10.61 ± 0.17）μm and a proportion of dead bacteria within the biofilm of（16.8 ± 0.8）%.③MEM-MBs were observed to penetrate into all layers of the biofilm using LSCM.④The results of crystal violet staining showed a decreasing trend in the biofilm density of the control group，the MEM group，the MEM-MBs group，the UTMD group，and the MEM-MBs+UTMD group. There was no significant difference between the MEM group and the MEM-MBs group（ P＞0.05），while there was a significant difference in biofilm density between the other groups，as revealed by pairwise comparison（all P＜0.05）.⑤UTMD technique and MEM-MBs+UTMD could significantly disrupt the biofilm of Escherichia coli. LSCM results showed that，compared to the control group，the thickness of the biofilm was reduced in all other groups，with only the UTMD group and the MEM-MBs+UTMD group showing an increase in porosity（both P＜0.05）. In comparison with the MEM group and the MEM-MBs group，the UTMD group showed an increase in porosity，while the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05）. Additionally，compared to the UTMD group，the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05），based on laser confocal microscopy results.⑥The results of the plate counting and LSCM showed that，compared with the control group，clump counts decreased，and the proportion of dead cells increased in the MEM group，the MEM-MBs group，and the MEM-MBs+UTMD group（all P＜0.05）. Compared with MEM group and MEM-MBs group，the clump counts of UTMD group increased，the proportion of dead cells decreased（all P＜0.05）；the clump counts of MEM-MBs+UTMD group decreased，and the proportion of dead cells increased（all P＜0.05）.Compared with UTMD group（all P＜0.05），the clump counts of MEM-MBs+UTMD group decreased，while the proportion of dead cells increased（all P＜0.05）.⑦The results of scanning electron microscopy revealed that the network structure of Escherichia coli was completely destroyed in the MEM-MBs+UTMD group. Conclusions:UTMD technology combined with MEM-MBs exerts a significant disruptive effect on the morphology and structure of Escherichia coli biofilm and significantly enhances bactericidal efficacy.

Objective:To investigate the essential determinants that are critical to initiating the assembly of outer membrane proteins by replacing the POTRA domains of the translocator protein FhaC and the insertase protein TtOmp85 of the Omp85 family. Methods:FhaC, TtOmp85 proteins and their recombinant chimeric proteins after replacing the POTRA domain were obtained by overexpression and purification in vitro. An in vitro reconstitution system was used to investigate the effects of the different domains on the transport efficiency of the substrate outer membrane protein FhaB and the membrane insertion efficiency of OmpA. Results:Replacing the POTRA domain of FhaC with that of TtOmp85 led to the loss of the transport function of FhaB. During the membrane insertion process of OmpA, the FhaC mutant containing the POTRA of TtOmp85 protein acquired the ability to assemble OmpA. Conclusion:The compositional differences in the POTRA domain of Omp85 family proteins determine their abilities to recognize their substrate proteins.

Objective:To systematically evaluate the safety and efficacy of the novel fibroblast activation protein (FAP)-targeted tracer 64Cu-FAP inhibitor (FAPI)-XT117 in patients with malignant solid tumors, and to compare with 18F-FDG. Methods:This self-controlled study was conducted on fifteen patients (8 males, 7 females; age (60 ±9) years) with malignant solid tumors from the First Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. Each subject underwent 64Cu-FAPI-XT117 PET/CT at 30, 60, and 120min post-injection and was assigned to three dose cohorts (111MBq, 148MBq, and 185MBq; 5 patients in each cohort), and safety assessments were conducted within 24h after injection. In addition, all patients underwent 18F-FDG PET/CT at 60min post-injection. Time-activity curves were generated for 64Cu-FAPI-XT117, and the dosimetry was calculated. Image quality was evaluated using a 5-point Likert scale, and the optimal injected activity and imaging time point were determined. The paired t test was used to compare differences of the lesion detection count and SUV max between 64Cu-FAPI-XT117 and 18F-FDG PET/CT. Results:64Cu-FAPI-XT117 was well tolerated, with no adverse events reported. Time-activity curves of 68Ga-FAPI-XT117 revealed prominent uptake in the uterus, while the background activity in other organs remained low, with the whole-body effective dose of (0.0084±0.0021)mSv/MBq. The optimal imaging time point for 64Cu-FAPI-XT117 PET/CT was 60min post-injection, with an optimal administered activity of 111MBq. Compared with 18F-FDG, 64Cu-FAPI-XT117 demonstrated significantly higher uptake and more lesions in lymph-node metastases (SUV max: 8.6±3.8 vs 15.3±6.8, t=2.33, P=0.048; number of lesions: 8.3±5.4 vs 15.0±6.4; t=4.21, P=0.003) and distant metastases (SUV max: 11.8±3.7 vs 20.9±7.2, t=3.66, P=0.022; number of lesions: 7.0±3.2 vs 12.4±3.7, t=2.86, P=0.046). Conclusions:64Cu-FAPI-XT117 PET/CT is well tolerated in patients with solid tumors, with a controllable radiation risk. Moreover, it outperforms 18F-FDG PET/CT in the assessment of metastases.

OBJECTIVE: To accurately measure human energy metabolism with high temporal resolution, a respiratory gas analysis system was designed using a breath-by-breath approach. METHODS: Firstly, indirect calorimetry was employed in respiratory gas analysis to measure the respiratory flow and concentration signals in real-time. Secondly, oxygen consumption QO2 and carbon dioxide production QCO2 were calculated through respiratory characteristic alignment and respiratory signal segmentation. Finally, metabolic indexes were calculated according to the Weir formula. Furthermore, a controlled trial was formulated for validation comparisons with the MGC ULTIMA SYSTEM PFX CARDIO2. RESULTS: The results indicate that the data points of metabolic indexes measured by this system all fall within the confidence interval when compared with those of the MGC. CONCLUSION The system has high consistency with the MGC measurement results. Thus, the system can accurately measure metabolism in real-time and provide data support for clinical nutrition assessment and therapy.
Humans ; Energy Metabolism ; Breath Tests/instrumentation* ; Calorimetry, Indirect/instrumentation* ; Equipment Design

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

Objective:To design an inspection system for quality of metabolism tester based on alcohol combustion mode for human body,so as to realize assessment for accuracy degree of human metabolism tester.Methods:According to the specific indicators that were measured by the metabolism tester for human body,a simulation of bidirectional controllable flow and a simulation of component concentration of exhaled breath were designed and realized.Then,the ratio of alcohol consumption to oxygen consumption and carbon dioxide production were calculated by the formula of alcohol combustion.Finally,the metabolic indexes(volume of gas flow,oxygen consumption,dioxide carbon production,rate of energy metabolism,respiratory quotient)that were outputted by the inspection system for quality were calculated according to Weir formula.Furthermore,the verification for precision of simulation modules of exhale and inhalation,and weighing device module was carried out,and an application test of inspection system for quality was also carried out.Results:The errors of the volume of gas flow and alcohol consumption that were outputted by simulation modules of exhale and inhalation,and weighing device module were all within±1%,and the errors between the reference value of the metabolic index of the inspection system for quality and the actually measured value of the metabolic index of the hood calorimeter were all within 10%.Conclusion:There was higher consistency between inspection system for quality of metabolism tester for human body and the actual measurement data of calorimeter,which can better simulate the process of respiratory metabolism of human body,and provide standardized testing means for the performance verification of metabolic tester.

Edema， as a common pathological phenomenon， is essentially the abnormal accumulation of body fluids in the interstitial spaces of human tissues and is often a direct manifestation of various underlying diseases， such as heart failure， impaired renal filtration function， or liver metabolic disorders. In the Western medical system， strategies for treating edema primarily focus on the use of diuretics to promote the excretion of excess fluid in the body， while simultaneously addressing the underlying causes through targeted treatment. However， long-term reliance on the use of diuretics may lead to a decrease in drug sensitivity and induce side effects， including electrolyte disorders such as hypokalemia and hypercalcemia， posing a potential threat to patients' overall health. Compared with Western medicine， traditional Chinese medicine （TCM） has demonstrated well-recognized and sustained efficacy in treating edema with its unique theoretical system. Zhulingtang， as a classic and commonly used TCM formula， is widely applied as it can effectively relieve edema and related symptoms. In recent years， ongoing in-depth studies on the treatment of edema with Zhulingtang have revealed multiple mechanisms of action of Zhulingtang， including the regulation of water metabolism and the reduction of inflammatory responses， thereby providing a solid theoretical basis for clinical practice. This review summarized the research progress on the treatment of edema with Zhulingtang in recent years and analyzed the active ingredients and action pathways of Zhulingtang. Additionally， the primary mechanisms of action and efficacy were systematically analyzed， so as to provide references for the clinical application of Zhulingtang in treating various types of edema， such as cardiogenic edema， renal edema， and hepatogenic edema. This review aims to offer theoretical support and practical guidance for clinicians in deciding treatment approaches， as well as references for subsequent in-depth studies， thereby promoting further development of TCM in the treatment of edema.

Edema， as a common pathological phenomenon， is essentially the abnormal accumulation of body fluids in the interstitial spaces of human tissues and is often a direct manifestation of various underlying diseases， such as heart failure， impaired renal filtration function， or liver metabolic disorders. In the Western medical system， strategies for treating edema primarily focus on the use of diuretics to promote the excretion of excess fluid in the body， while simultaneously addressing the underlying causes through targeted treatment. However， long-term reliance on the use of diuretics may lead to a decrease in drug sensitivity and induce side effects， including electrolyte disorders such as hypokalemia and hypercalcemia， posing a potential threat to patients' overall health. Compared with Western medicine， traditional Chinese medicine （TCM） has demonstrated well-recognized and sustained efficacy in treating edema with its unique theoretical system. Zhulingtang， as a classic and commonly used TCM formula， is widely applied as it can effectively relieve edema and related symptoms. In recent years， ongoing in-depth studies on the treatment of edema with Zhulingtang have revealed multiple mechanisms of action of Zhulingtang， including the regulation of water metabolism and the reduction of inflammatory responses， thereby providing a solid theoretical basis for clinical practice. This review summarized the research progress on the treatment of edema with Zhulingtang in recent years and analyzed the active ingredients and action pathways of Zhulingtang. Additionally， the primary mechanisms of action and efficacy were systematically analyzed， so as to provide references for the clinical application of Zhulingtang in treating various types of edema， such as cardiogenic edema， renal edema， and hepatogenic edema. This review aims to offer theoretical support and practical guidance for clinicians in deciding treatment approaches， as well as references for subsequent in-depth studies， thereby promoting further development of TCM in the treatment of edema.