Single-cell RNA sequencing and cell-cell communication analysis reveal tumor microenvironment associated with chemotherapy responsiveness in ovarian cancer.

BACKGROUND: To investigate the impact of the tumor microenvironment (TME) on the responsiveness to chemotherapy in ovarian cancer (OV). METHODS: We integrated single cell RNA-seq datasets of OV containing chemo-response information, and characterize their clusters based on different TME sections. We focus on analyzing cell-cell communication to elaborate on the mechanisms by which different components of the TME directly influence the chemo-response of tumor cells. RESULTS: scRNA-seq datasets were annotated according to specific markers for different cell types. Differential analysis of malignant epithelial cells revealed that chemoresistance was associated with the TME. Notably, distinct TME components exhibited varying effects on chemoresistance. Enriched SPP1+ tumor-associated macrophages in chemo-resistant patients could promote chemoresistance through SPP1 binding to CD44 on tumor cells. Additionally, the overexpression of THBS2 in stromal cells could promote chemoresistance through binding with CD47 on tumor cells. In contrast, GZMA in the lymphocytes could downregulate the expression of PARD3 through direct interaction with PARD3, thereby attenuating chemoresistance in tumor cells. CONCLUSION: Our study indicates that the non-tumor cell components of the TME (e.g. SPP1+ TAMs, stromal cells and lymphocytes) can directly impact the chemo-response of OV and targeting the TME was potentially crucial in chemotherapy of OV.

Effects of dental tissue substructure and size on fracture strengths of lithium disilicate and zirconia ceramics

We aimed to assess the effects of standard resin preparation models with five different thicknesses of occlusal surface on the fracture strengths of zirconia (ZrO2) and lithium disilicate glass ceramics. The specimens of 10 first maxillary molars collected between January 2019 and January 2020 were selected. Standard mathematical models were formed after scanning the resin matrices using software. The full crowns with five different thicknesses of occlusal surface were established, among which the molar specimens prepared by ZrO2 glass ceramic composites alone were assigned into ZrO2 group (n=5, 40 specimens) while those prepared using ZrO2-lithium disilicate glass ceramic composites were allocated into ZTCLDC group (n=5, 40 specimens). When the thickness of glass-ceramic full crowns was 0.5, 0.8, 1.0, 1.2 and 1.5 mm, the fracture load of the specimens in ZTCLDC group was not significantly different from that in ZrO2 group, and there was no significant difference in the three-point flexural strength between ZTCLDC group and ZrO2 group (P>0.05). The fracture toughness was not significantly different between the two groups in the case of the thickness of glass-ceramic full crown at 0.5, 0.8, 1.0, 1.2 and 1.5 mm (P>0.05). The thickness was positively correlated with fracture load, three-point flexural strength and fracture toughness (P<0.05). The fracture strength of lithium disilicate and ZrO2 ceramics is directly proportional to the thickness of ZrO2 and ZTCLDC crowns.

Paeoniflorin mitigates PBC-induced liver fibrosis by repressing NLRP3 formation.

PURPOSE: To delve into the influence of paeoniflorin (PA) on abating primary biliary cholangitis (PBC)-induced liver fibrosis and its causative role. METHODS: Our team allocated the mice to control group, PA group, PBC group and PBC+PA group. We recorded the weight change of mice in each group. We used Masson staining for determining liver fibrosis, immunofluorescence staining for measuring tumor necrosis factor-α (TNF-α) expression, quantitative real-time polymerase chain reaction (qRT-PCR) for assaying related gene expression, as well as Western blot for testing related protein expression. RESULTS: The weight of PBC model mice declined. Twenty-four weeks after modeling, the positive rate of anti-mitochondrial antibody-M2 (AMA-M2) in PBC mice reached 100%. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxyproline (HYP), laminin (LN), procollagen type III (PC III), and malondialdehyde (MDA) contents saliently waxed (p<0.01). Meanwhile, superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity patently waned (p<0.01). Liver fibrosis levels were flagrantly higher (p<0.01), and TNF-α, NOD-like receptor protein 3 (NLRP3), caspase-1, interleukin-18 (IL-18), and interleukin-1ß (IL-1ß) protein or gene expression were manifestly up-regulated (p<0.01). PA could restore the weight of PBC mice, strikingly restrain the positive expression of AMA-M2, and down-regulate serum ALP, ALT, AST, HYP, LN, PC III, MDA in PBC mice (p<0.01). PA could also significantly up-regulate SOD and GSH-px levels (p<0.01), down-regulate IL-1ß, IL-18, caspase-1, NLRP3, and TNF-α protein or gene expression in PBC mice (p<0.01) and inhibit liver fibrosis levels (p<0.01). CONCLUSIONS: PA can reduce PBC-induced liver fibrosis in mice and may function by curbing the formation of NLRP3.

Paeoniflorin mitigates PBC-induced liver fibrosis by repressing NLRP3 formation

ABSTRACT Purpose: To delve into the influence of paeoniflorin (PA) on abating primary biliary cholangitis (PBC)-induced liver fibrosis and its causative role. Methods: Our team allocated the mice to control group, PA group, PBC group and PBC+PA group. We recorded the weight change of mice in each group. We used Masson staining for determining liver fibrosis, immunofluorescence staining for measuring tumor necrosis factor-α (TNF-α) expression, quantitative real-time polymerase chain reaction (qRT-PCR) for assaying related gene expression, as well as Western blot for testing related protein expression. Results: The weight of PBC model mice declined. Twenty-four weeks after modeling, the positive rate of anti-mitochondrial antibody-M2 (AMA-M2) in PBC mice reached 100%. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxyproline (HYP), laminin (LN), procollagen type III (PC III), and malondialdehyde (MDA) contents saliently waxed (p<0.01). Meanwhile, superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity patently waned (p<0.01). Liver fibrosis levels were flagrantly higher (p<0.01), and TNF-α, NOD-like receptor protein 3 (NLRP3), caspase-1, interleukin-18 (IL-18), and interleukin-1β (IL-1β) protein or gene expression were manifestly up-regulated (p<0.01). PA could restore the weight of PBC mice, strikingly restrain the positive expression of AMA-M2, and down-regulate serum ALP, ALT, AST, HYP, LN, PC III, MDA in PBC mice (p<0.01). PA could also significantly up-regulate SOD and GSH-px levels (p<0.01), down-regulate IL-1β, IL-18, caspase-1, NLRP3, and TNF-α protein or gene expression in PBC mice (p<0.01) and inhibit liver fibrosis levels (p<0.01). Conclusions: PA can reduce PBC-induced liver fibrosis in mice and may function by curbing the formation of NLRP3.

Characteristics of groundwater discharge to river and related heavy metal transportation in a mountain mining area of Dabaoshan, Southern China.

Groundwater discharge to river and the related heavy metal transportation were estimated for Dabaoshan, a mountain mining area where extensive mining activities had been conducted over 40 years. In the lower reach of the mining area, shallow aquifers were contaminated by varies heavy metals due to the discharge of acid mine drainage. Polluted aquifers act as long-term pollution sources to the surrounding gaining rivers, even after the mining activities were stopped. The natural tracer 222Rn was measured for river water of the Hengshi River and groundwater adjacent to the river channel in both wet and dry seasons. The total groundwater discharge rate was estimated to be 17.4-26.7 × 103 m3 day-1 in wet season and 1.9-2.1 × 103 m3 day-1 in dry season; and the river recharge was 5.6 ±â€¯1.0 × 103 m3 day-1 in wet season and 2.1 ±â€¯1.0 × 103 m3 day-1 in dry season. Compared with other mining and natural/artificial factor influenced areas, groundwater discharge rate in Dabaoshan was much lower, but the magnitudes of groundwater-borne Cu, Zn, Mn and Co fluxes were comparable or even much higher. This suggested that groundwater-derived heavy metal fluxes were significant pollution sources to river in the mountain mining area. Meanwhile, the results also suggested that concentrations of Cd, Pb, Cu, Ni, Mn, Fe, Zn and Tl in groundwater increased where the recharge of river water to groundwater occurred, suggesting the recharge of river water can affect heavy metal concentrations of the beneath aquifers, even in a gaining river.

Contributions of Zea mays subspecies mexicana haplotypes to modern maize.

Maize was domesticated from lowland teosinte (Zea mays ssp. parviglumis), but the contribution of highland teosinte (Zea mays ssp. mexicana, hereafter mexicana) to modern maize is not clear. Here, two genomes for Mo17 (a modern maize inbred) and mexicana are assembled using a meta-assembly strategy after sequencing of 10 lines derived from a maize-teosinte cross. Comparative analyses reveal a high level of diversity between Mo17, B73, and mexicana, including three Mb-size structural rearrangements. The maize spontaneous mutation rate is estimated to be 2.17 × 10-8 ~3.87 × 10-8 per site per generation with a nonrandom distribution across the genome. A higher deleterious mutation rate is observed in the pericentromeric regions, and might be caused by differences in recombination frequency. Over 10% of the maize genome shows evidence of introgression from the mexicana genome, suggesting that mexicana contributed to maize adaptation and improvement. Our data offer a rich resource for constructing the pan-genome of Zea mays and genetic improvement of modern maize varieties.

Clinical Analysis of Polyethylene Glycol Interferon-α Treatment in 155 Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB) Patients.

PURPOSE: This study aims to investigate the antiviral effect of polyethylene glycol (PEG)-interferon α-2a and PEG-interferon α-2b treatment on hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) at the 48th week of treatment and the 24th and 48th week after withdrawal, in order to provide guidance on the antiviral treatment of HBeAg-positive CHB patients. MATERIAL AND METHODS: Antiviral treatment was performed on 155 HBeAg-positive CHB patients. Among these patients, 66 patients received PEG-interferon α-2a treatment and 89 patients received PEG-interferon α-2b treatment; and these treatments were administered by subcutaneous injection, once per week, which lasted for 48 weeks. Other antiviral and hepatoprotective drugs were not used during the treatment. RESULTS: At the 48th week of treatment, ALT recovery rate, HBsAg seroconversion rate, HBeAg seroconversion rate and HBV DNA titers dropped below 200 IU/mL rate were 69.7%, 6.1%, 27.3% and 50.0%, respectively, in the PEG-interferon α-2a group; and were 70.8%, 6.7%, 33.7% and 62.9%, respectively, in the PEG-interferon α-2b group. At the 24th and 48th week of follow-up after withdrawal, HBsAg seroconversion rate in these two groups did not change; and HBeAg seroconversion rate further increased. Furthermore, HBV DNA revealed a low recurrence rate. The difference between these two groups was not significantly significant. CONCLUSIONS: PEG-interferon α-2a and PEG-interferon α-2b are effective antiviral drugs for the treatment of HbeAgpositive CHB, which has a HBsAg seroconversion rate of more than 5%. Furthermore, this sustained response effect was maintained at the 24th and 48th week of follow-up after withdrawal.