OBJECTIVE To explore the effect and mechanism of embryonic intervention with Zuogui pill on the glucose tolerance in offsprings of pregnant rats with gestational diabetes mellitus. METHODS Pregnant rats were randomly divided into blank group， model group， positive control group （insulin glargine）， Zuogui pill low-， medium- and high-dose groups （4.725， 9.45， 18.9 g/kg）. In addition to the blank group， streptozotocin was injected intraperitoneally to establish a gestational diabetes mellitus rat model. From day 6 to day 18 of pregnancy， each group was given relevant medicine and distilled water intragastrically， once a day. After 21 days of birth， the body weight and body length of offsprings were recorded， and the area under the curve （AUC） was calculated through a glucose tolerance test. After 22 days of birth， fasting blood glucose （FBG）， fasting insulin （FINS） levels in serum， insulin sensitivity index （ISI）， and homeostasis model assessment of insulin resistance （HOMA-IR） were measured， and the morphological structure of pancreatic tissue was observed. The protein spectrum of pancreatic tissue was analyzed by tandem mass tag-based proteomics， and protein and mRNA expression levels of apolipoprotein A1（ApoA1）， solute carrier family 27 member 1 （Slc27a1）， kininogen 1（Kng1） and sodium/potassium-transporting ATPase subunit alpha 2 （Atp1a2）， solute carrier family 7 member 5 （Slc7a5）， solute carrier family 3 member 2 （Slc3a2）， bile acid-coenzyme A： amino acid N- acyltransferase （Baat）， eukaryotic translation initiation factor 2 subunit gamma （Eif2s3） were detected. RESULTS Compared with the model group， the body weight， body length and ISI of offsprings in the positive control group and Zuogui pill medium-dose group were significantly increased （P＜0.05）， while the glucose tolerance and islet cell proliferation were significantly improved， and the AUC， FBG， FINS and HOMA-IR were significantly decreased （P＜0.05）. There were 88 potential target proteins for the embryonic intervention of Zuogui pill in offsprings of pregnant rats with gestational diabetes mellitus，involving multiple pathways such as peroxisome proliferator-activated receptor （PPAR）， cyclic guanosine monophosphate-protein kinase G （cGMP-PKG）， fat digestion and absorption， and bile secretion. The proteins closely related to glucose metabolism and insulin resistance mainly included ApoA1， Slc27a1， Kng1， Atp1a2， Slc7a5， Slc3a2， Baat， and Eif2s3. Among them， compared with the model group， protein and mRNA expressions of Slc7a5， Slc3a2， and Baat in the pancreatic tissues of pregnant rat offsprings in the Zuogui pill medium-dose group were significantly up-regulated （P＜0.05）； protein and mRNA expressions of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 were all significantly down-regulated （P＜0.05）. CONCLUSIONS The intervention of Zuogui pill in the embryonic period on offsprings of pregnant rats with gestational diabetes mellitus can improve their blood glucose levels and pancreatic pathological morphology. The mechanism may be related to the upregulation of the expressions of Slc7a5， Slc3a2， and Baat and the down-regulation of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 expressions in the PPAR， cGMP-PKG， fat digestion and absorption， and bile secretion pathways.

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L^-1, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L^-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry* ; Humans ; Sesquiterpenes/isolation & purification* ; Cell Line, Tumor ; Molecular Structure ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/pharmacology* ; Drug Resistance, Multiple/drug effects* ; Molecular Docking Simulation

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

BACKGROUND:The occurrence of neuronal axonal injury can result in neurological dysfunction,and the facilitation of axonal elongation is anticipated to play a pivotal role in the treatment of diseases affecting the nervous system.OBJECTIVE:To investigate whether ectomesenchymal stem cells-derived extracellular vesicles can promote neuronal axonal elongation.METHODS:(1)Ectomesenchymal stem cells were obtained from nasal mucosa using the tissue adherence method,and the specific markers of were identified through immunofluorescence.Ectomesenchymal stem cells-derived extracellular vesicles were acquired via ultracentrifugation and identified.(2)Ectomesenchymal stem cells-derived extracellular vesicles(0,0.5,1.0,1.5 mg/mL)were incubated with PC12 cells for 72 hours.The cytotoxicity and proliferation of ectomesenchymal stem cells-derived extracellular vesicles on PC12 cells were assessed using the CCK-8 assay.(3)Ectomesenchymal stem cells-derived extracellular vesicles(1.0 mg/mL)were incubated with PC12 cells or neurons for 72 hours.The changes in axon length were observed using microscopic analysis.The expression levels of axon-related markers β3-tubulin(early stage),growth associated protein 43(middle stage),and neurofilament 200(mature stage)were analyzed through real-time fluorescence quantitative PCR and Western blotting.These investigations aimed to explore the potential of ectomesenchymal stem cells-derived extracellular vesicles in promoting neurite elongation within PC12 cells or neurons.RESULTS AND CONCLUSION:(1)The majority of the acquired ectomesenchymal stem cells exhibited a spindle-shaped morphology,while a minority displayed irregular shapes,and demonstrated high expression levels of mesenchymal stem cell-specific markers Nestin,CD44,and Vimentin.The obtained ectomesenchymal stem cells-derived extracellular vesicles fulfilled the biological criteria for extracellular vesicles.(2)Within the detected protein concentration range of 0.5 to 1.5 mg/mL,the proliferation of PC12 cells was promoted by ectomesenchymal stem cells-derived extracellular vesicles,and this effect was further enhanced with increasing concentrations.(3)Ectomesenchymal stem cells-derived extracellular vesicles increased the length of axons in PC12 cells and neurons and the expression of axon-related markers β3-tubulin,growth associated protein 43,and neurofilament 200.Above findings suggest that ectomesenchymal stem cells-derived extracellular vesicles have the potential to enhance neuronal axonal elongation.

BACKGROUND:The occurrence of neuronal axonal injury can result in neurological dysfunction,and the facilitation of axonal elongation is anticipated to play a pivotal role in the treatment of diseases affecting the nervous system.OBJECTIVE:To investigate whether ectomesenchymal stem cells-derived extracellular vesicles can promote neuronal axonal elongation.METHODS:(1)Ectomesenchymal stem cells were obtained from nasal mucosa using the tissue adherence method,and the specific markers of were identified through immunofluorescence.Ectomesenchymal stem cells-derived extracellular vesicles were acquired via ultracentrifugation and identified.(2)Ectomesenchymal stem cells-derived extracellular vesicles(0,0.5,1.0,1.5 mg/mL)were incubated with PC12 cells for 72 hours.The cytotoxicity and proliferation of ectomesenchymal stem cells-derived extracellular vesicles on PC12 cells were assessed using the CCK-8 assay.(3)Ectomesenchymal stem cells-derived extracellular vesicles(1.0 mg/mL)were incubated with PC12 cells or neurons for 72 hours.The changes in axon length were observed using microscopic analysis.The expression levels of axon-related markers β3-tubulin(early stage),growth associated protein 43(middle stage),and neurofilament 200(mature stage)were analyzed through real-time fluorescence quantitative PCR and Western blotting.These investigations aimed to explore the potential of ectomesenchymal stem cells-derived extracellular vesicles in promoting neurite elongation within PC12 cells or neurons.RESULTS AND CONCLUSION:(1)The majority of the acquired ectomesenchymal stem cells exhibited a spindle-shaped morphology,while a minority displayed irregular shapes,and demonstrated high expression levels of mesenchymal stem cell-specific markers Nestin,CD44,and Vimentin.The obtained ectomesenchymal stem cells-derived extracellular vesicles fulfilled the biological criteria for extracellular vesicles.(2)Within the detected protein concentration range of 0.5 to 1.5 mg/mL,the proliferation of PC12 cells was promoted by ectomesenchymal stem cells-derived extracellular vesicles,and this effect was further enhanced with increasing concentrations.(3)Ectomesenchymal stem cells-derived extracellular vesicles increased the length of axons in PC12 cells and neurons and the expression of axon-related markers β3-tubulin,growth associated protein 43,and neurofilament 200.Above findings suggest that ectomesenchymal stem cells-derived extracellular vesicles have the potential to enhance neuronal axonal elongation.

Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

A 65-year-old male was admitted because of anorexia, gross hematuria, skin purpura and acute renal insufficiency. Cardiovascular interventional examination was performed in other hospital 3 months before admission. During hospitalization, multiple blood cultures suggested positive Streptococcus gordonii, decreased blood complement and increased rheumatoid factor. Echocardiography revealed mitral valve vegetations (4 mm), and renal biopsy revealed endocapillary proliferative glomerulonephritis, diagnosed as infective endocarditis-associated glomerulonephritis. The combination of effective antibiotics and plasma exchange therapy significantly improved clinical symptoms and acute renal failure. The case suggests that plasma exchange is effective and safe in the treatment of immune complex-mediated glomerulonephritis caused by infective endocarditis, providing a new option for the treatment of such diseases.

Oxidative stress plays a key role in acute kidney injury (AKI). 8-Oxo-7,8-dihydroguanosine (8-oxo-Gsn) can reflect the overall level of oxidative stress in the body. The levels of urinary 8-oxo-Gsn and renal function-related indicators in 62 patients who underwent video-assisted thoracic surgery (VATS) or open-chest surgery were measured during the perioperative period. The results showed that urinary 8-oxo-Gsn increased 24 hours after surgery and decreased 48 hours after surgery as the condition improved. In 10 patients with severe complications, urinary 8-oxo-Gsn continued to rise. The level of urinary 8-oxo-Gsn in the VATS group recovered faster than that in the open-chest surgery group ( P<0.05). There was a certain correlation between the level of urinary 8-oxo-Gsn and postoperative renal injury in thoracic surgery, suggesting that RNA oxidative stress may play an important role in the pathogenesis of surgery-related AKI.