Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

This article aims to explore the effect and mechanism of Liujunzi Pills on the intestinal microbiota of rats with spleen Qi deficiency syndrome. The raw Rhei Radix et Rhizoma water extract(1 g·mL~(-1)) was used to prepare spleen Qi deficiency rat models. A total of 44 SD male rats were randomly divided into a control group, a model group, Liujunzi Pills groups at high(3.24 g·kg~(-1)), medium(1.62 g·kg~(-1)), low(0.81 g·kg~(-1)) doses, and Shenling Baizhu San(2.50 g·kg~(-1)) group. The drug effect was evaluated by observing the following aspects: spleen index, fecal water content, body weight, and intestinal propulsion index. Gut microbiota analysis and 16S rRNA gene sequencing were conducted on feces. Enzyme-linked immunosorbent assay(ELISA) and UV spectrophotometry were used to detect interleukin-1β(IL-1β) and adenosine triphosphate(ATP) levels in small intestine tissues. Hematoxylin-eosin staining and transmission electron microscopy were employed to observe changes in intestinal pathology and microstructure. The results show that, compared with the control group, fecal moisture content is significantly increased while spleen index, body weight, and intestinal propulsion index are significantly reduced in rats of the model group, indicating the successful establishment of the model. The above symptoms can be improved by both Shenling Baizhu San and Liujunzi Pills. Compared with the control group, in the model group, the gut microbiota abundance is changed with an unbalanced development: the abundance of beneficial bacteria within the Bacteroidetes phylum is reduced, accompanied by a significantly decreased Shannon index, and reduced signal levels of nicotinamide adenine dinucleotide phosphate(NADPH)-related enzymes relevant to mitochondria. However, Liujunzi Pills and Shenling Baizhu San can significantly improve the Bacteroidetes phylum abundance in gut microbiota, microbial diversity, and NADPH activity in the model group. Additionally, compared with the control group, the ATP level is decreased and the IL-1β level is increased in small intestinal tissues of the model group, with shorter small intestinal epithelial villi and decreased mitochondrial number. The above symptoms can be improved by Liujunzi Pills and Shenling Baizhu San. In conclusion, Liujunzi Pills can treat spleen Qi deficiency syndrome by enhancing mitochondrial function to regulate gut microbiota balance and diversity.
Animals ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Rats, Sprague-Dawley ; Rats ; Qi ; Spleen/metabolism* ; Splenic Diseases/metabolism* ; Humans ; Interleukin-1beta/genetics* ; Bacteria/drug effects* ; Feces/microbiology* ; Adenosine Triphosphate/metabolism*

OBJECTIVES: To investigate the molecular mechanism by which He's Yangchao Formula improves ovarian function in premature ovarian insufficiency (POI) mice through intestinal flora modulation. METHODS: Forty female ICR mice (aged 6-8 weeks) were intraperitoneally injected with cyclophosphamide (150 mg/kg) to establish a POI model, while 10 untreated mice served as the blank control. Successfully modeled mice were randomly divided into four groups (n=10/group): low-dose He's Yangchao Formula (6 g crude herb/kg), high-dose He's Yangchao Formula (25 g crude herb/kg), positive control (estradiol), and model control (distilled water). Treatments were admin-istered daily by gavage for 6 weeks. Vaginal exfoliated cells were stained with Wright-Giemsa solution to monitor estrous cycles. Serum estradiol and follicle-stimulating hormone (FSH) levels were measured by ELISA. Ovarian FSH receptor (FSHR) expression was assessed by immunohistochemistry. Glycolysis-related proteins pyruvate kinase M2 (PKM2) and glucose transporter 4 (GLUT4) were analyzed by Western blotting and immuno-fluorescence. Fecal samples from blank control, model control, and high-dose groups underwent metagenomic sequencing to evaluate intestinal microbiota diversity and com-position. RESULTS: He's Yangchao Formula restored estrous cyclicity, increased serum estradiol (P<0.05), decreased serum FSH (P<0.05), and upregulated FSHR expression in granulosa cells (P<0.05). Metagenomic analysis revealed significant structural differences in intestinal flora among blank control, model control, and high-dose groups (P<0.01). The high-dose group showed reduced abundance of conditional pathogens (e.g., Alistipes, Prevotella, Odoribacter, Blautia, Rikenella) compared to the model control (P<0.05). Functional enrichment analysis indicated involvement of glycolysis-related pathways. Concordantly, PKM2 and GLUT4 expression was downregulated in the model control but upregulated in He's Yangchao Formula groups (P<0.05). CONCLUSIONS He's Yangchao Formula ameliorates POI in mice by remodeling intestinal flora structure, enhancing glycolytic activity, improving ovarian sex hormone secretion, increasing granulosa cell FSHR expression, and restoring estrous cyclicity.

OBJECTIVES: To investigate the molecular mechanism by which He's Yangchao Decoction (HSYC) improves ovarian function in a mouse model of premature ovarian insufficiency (POI). METHODS: Forty ICR mice were used to establish a POI model via intraperitoneal injection of cyclophosphamide and were randomly assigned to four groups: model control group, low-dose HSYC group, high-dose HSYC group, and estradiol group (positive control). Additionally, 10 age-matched ICR mice were selected as the blank control group. After intragastric intervention, the ovarian index, serum follicle-stimulating hormone (FSH) levels, and ovarian tissue expression of the FSH receptor (FSHR) were measured. A POI cell model was established by treating the human granulosa tumor cell line (KGN) with 4-hydroxycyclophosphamide. The cells were divided into four groups: solvent control group, HSYC group, inhibitor control group, and inhibitor+HSYC group, which were respectively treated with TH5487 (an OGG1 inhibitor) and HSYC-containing serum. The expressions of OGG1, mitochondrial DNA (mtDNA) oxidative damage markers, and pyroptosis-related proteins were detected by molecular docking, Western blotting, and immunofluorescence. RESULTS: Compared with the blank control group, the model control group showed a decreased ovarian index (P<0.05) and increased serum FSH levels (P<0.01). The ovarian index was higher in both the low- and high-dose HSYC groups compared with the model control group (both P<0.05). FSHR expression in ovarian tissue was lower in the model control group than that in the blank control group, but was higher in the high-dose HSYC group compared with the model control group (P<0.05 or P<0.01). Molecular docking confirmed strong binding affinity between the active components of HSYC and OGG1 (binding energy: －6.3 to －8.3 kcal/mol). Western blotting analysis revealed that OGG1 protein expression in the ovaries of the model control group was significantly reduced compared with the blank control group, while it was increased in the low-dose HSYC group and the estradiol group (P<0.05 or P<0.01). Immunofluorescence results demonstrated that the expression levels of mito-chondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) were decreased in the model control group compared with the blank control group (P<0.01), whereas their expressions were significantly elevated in the high-dose HSYC group and the estradiol group (all P<0.01). Cell experiments showed that TH5487 intervention increased the expression of 8-oxoguanine (8-OxoG) (P<0.01), while HSYC-containing serum intervention reduced 8-OxoG expression and increased TFAM expression (P<0.01). The expression of pyroptosis-related proteins (GSDMD, N-GSDMD, caspase-1, IL-1β) increased after TH5487 intervention (P<0.05), whereas HSYC-containing serum suppressed their expression (all P<0.05). CONCLUSIONS HSYC improves POI by upregulating OGG1 expression, mitigating mtDNA oxidative damage, and inhibiting granulosa cell pyroptosis.

(±)-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*

As global greenhouse gases continue rising, the urgency of more ambitious action is clearer than ever before. China is the world's biggest emitter of greenhouse gases and one of the countries affected most by climate change. The evidence about the impacts of climate change on the environment and human health may encourage China to take more decisive action to mitigate greenhouse gas emissions and adapt to climate impacts. This article aimed to review the evidence of environmental damages and health risks posed by climate change and to provide a new science-based perspective for the delivery of sustainable development goals. Over recent decades, China has experienced a strong warming pattern with a growing frequency of extreme weather events, and the impacts of climate change on China's environment and human health have been consistently observed, with increasing O ₃ air pollution, decreases in water resources and availability, land degradation, and increased risks for both communicable and non-communicable diseases. Therefore, China's climate policy should target the key factors driving climate change and scale up strategic measures to curb carbon emissions and adapt to inevitable increasing climate impacts. It provides new insights for not only China but also other countries, particularly developing and emerging economies, to ensure climate and environmental sustainability whilst pursuing economic growth.
Climate Change ; China ; Humans ; Greenhouse Gases ; Air Pollution ; Sustainable Development ; Environment

To develop a method for determining the antibody-dependent cell-mediated phagocytosis (ADCP) activity of human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate (ADC) based on the reporter gene assay, we established an ADCP activity assay with Jurkat/NFAT/FcγRIIa cells as the effector cells and BT474 as the target cells. Then, the target cell density, the ratio of effector to target cells, the target cell adhesion time, the incubation time for drug administration, and the induction time after adding effector cells were optimized by the method of design of experiment (DOE). The method showed a significant dose-response relationship, which was complied with the four-parameter equation: y=(A-D)/[1+(x/C)^B]+D. The durability ranges of the target cell density, the ratio of effector to target cells, the target cell adhesion time, the incubation time for drug administration, and the induction time after adding effector cells were (2.5-4.0)×10⁵ cells/mL, 3-5, 1.0-2.0 h, 0 h, and 5.0-6.0 h, respectively. The results of the methodological validation showed that the linear equation was y=1.106 8x-0.011 6, r=0.969 2. The established method showed the relative accuracy ranging from -6.59% to 2.98% and the geometric coefficient of variation less than 11% in the intermediate precision test. Furthermore, the method was target-specific. The method was then applied to the determination of ADCP activity of HER2-targeted ADC, demonstrating the result of (103.5±5.7)%. We developed a reporter gene assay for determining the ADCP activity of HER2-targeted ADC and the assay demonstrated high accuracy and good reproducibility, which proposes a highly efficient and approache for evaluating ADCP effect of this HER2-targeted ADC, and also provides a referable technique for characterizing the Fc effector functions of ADCs with diverse targets.
Humans ; Receptor, ErbB-2/immunology* ; Phagocytosis/drug effects* ; Immunoconjugates/immunology* ; Genes, Reporter ; Antibody-Dependent Cell Cytotoxicity ; Jurkat Cells

The early response of plant auxin gene family Aux/IAA (auxin/indole-3-acetic acid) and its interaction with auxin response factor (ARF) are important pattern to regulate plant growth and development. This work identified 28 StoIAA and 24 StoARF members based on the whole genome data of the medicinal plant Senna tora L., which were classified into 10 and 8 subfamilies, respectively. Phylogenetic tree and collinearity analysis showed that S. tora has close evolutionary relationship with the IAA and ARF homologous genes of Glycine max, Medicago truncatula, and the segment duplication events dominate the expansion of StoIAA and StoARF. Gene structure analysis showed that the vast majority of StoIAA and StoARF contain characteristic conserved domain. Transcriptome data showed that StoIAAs and StoARFs were expressed in leaves, roots and seeds, some members had tissue specific expression. The StoIAA and StoARF promoter region most contain functional elements related to stress response, growth and development, hormone induction and secondary metabolism. In addition, gene expression analysis showed that many StoIAAs and StoARFs can quickly respond to drought and salt stress and exhibited same expression patterns under both stress condition. The yeast two-hybrid experiment confirmed that StoARF8 and StoARF10 exhibit varying degrees of interaction with multiple StoIAA proteins, respectively. The above results provide a basis for further biological functional analysis of the Aux/IAA and ARF gene family of S. tora.