Melatonin as an immunomodulator in CD19-targeting CAR-T cell therapy: managing cytokine release syndrome.

BACKGROUND: Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment resistance or relapse. However, the emergence of cytokine release syndrome (CRS) as a side effect poses a challenge to the widespread application of CAR-T cell therapies. Melatonin, a natural hormone produced by the pineal gland known for its antioxidant and anti-inflammatory properties, has been explored for its potential immunomodulatory effects. Despite this, its specific role in mitigating CAR-T cell-induced CRS remains poorly understood. METHODS: In this study, our aim was to investigate the potential of melatonin as an immunomodulatory agent in the context of CD19-targeting CAR-T cell therapy and its impact on associated side effects. Using a mouse model, we evaluated the effects of melatonin on CAR-T cell-induced CRS and overall survival. Additionally, we assessed whether melatonin administration had any detrimental effects on the antitumor efficacy and persistence of CD19 CAR-T cells. RESULTS: Our findings demonstrate that melatonin effectively mitigated the severity of CAR-T cell-induced CRS in the mouse model, leading to improved overall survival outcomes. Remarkably, melatonin administration did not compromise the antitumor effectiveness or persistence of CD19 CAR-T cells, indicating its compatibility with therapeutic goals. These results suggest melatonin's potential as an immunomodulatory compound to alleviate CRS without compromising the therapeutic benefits of CAR-T cell therapy. CONCLUSION: The study's outcomes shed light on melatonin's promise as a valuable addition to the existing treatment protocols for CAR-T cell therapies. By attenuating CAR-T cell-induced CRS while preserving the therapeutic impact of CAR-T cells, melatonin offers a potential strategy for optimizing and refining the safety and efficacy profile of CAR-T cell therapy. This research contributes to the evolving understanding of how to harness immunomodulatory agents to enhance the clinical application of innovative cancer treatments.

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate Enhances foxo1-Mediated Lipophagy to Remodel Lipid Metabolism in Zebrafish Liver.

An emerging environmental contaminant, bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), can bioaccumulate in the liver and affect hepatic lipid metabolism. However, the in-depth mechanism has yet to be comprehensively explored. In this study, we utilized transgenic zebrafish Tg (Apo14: GFP) to image the interference of TBPH on zebrafish liver development and lipid metabolism at the early development stage. Using integrated lipidomic and transcriptomic analyses to profile the lipid remodeling effect, we uncovered the potential effects of TBPH on lipophagy-related signaling pathways in zebrafish larvae. Decreased lipid contents accompanied by enhanced lipophagy were confirmed by the measurements of Oil Red O staining and transmission electron microscopy in liver tissues. Particularly, the regulatory role of the foxo1 factor was validated via its transcriptional inhibitor. Double immunofluorescence staining integrated with biochemical analysis indicated that the enhanced lipophagy and mitochondrial fatty acid oxidation induced by TBPH were reversed by the foxo1 inhibitor. To summarize, our study reveals, for the first time, the essential role of foxo1-mediated lipophagy in TBPH-induced lipid metabolic disorders and hepatoxicity, providing new insights for metabolic disease studies and ecological health risk assessment of TBPH.

Mechanistic Insights into 1,2-bis(2,4,6-tribromophenoxy)ethane-Induced Male Reproductive Toxicity in Zebrafish.

The novel brominated flame retardant, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), has increasingly been detected in environmental and biota samples. However, limited information is available regarding its toxicity, especially at environmentally relevant concentrations. In the present study, adult male zebrafish were exposed to varying concentrations of BTBPE (0, 0.01, 0.1, 1, and 10 µg/L) for 28 days. The results demonstrated underperformance in mating behavior and reproductive success of male zebrafish when paired with unexposed females. Additionally, a decline in sperm quality was confirmed in BTBPE-exposed male zebrafish, characterized by decreased total motility, decreased progressive motility, and increased morphological malformations. To elucidate the underlying mechanism, an integrated proteomic and phosphoproteomic analysis was performed, revealing a predominant impact on mitochondrial functions at the protein level and a universal response across different cellular compartments at the phosphorylation level. Ultrastructural damage, increased expression of apoptosis-inducing factor, and disordered respiratory chain confirmed the involvement of mitochondrial impairment in zebrafish testes. These findings not only provide valuable insights for future evaluations of the potential risks posed by BTBPE and similar chemicals but also underscore the need for further research into the impact of mitochondrial dysfunction on reproductive health.

Aurantio-obtusin Alleviates Dry Eye Disease by Targeting NF-κB/NLRP3 Signaling in Rodent Models.

Dry eye disease (DED) is a common inflammatory ocular surface disorder, seriously affecting the quality of life of patients. Aurantio-obtusin (AO) is a bioactive anthraquinone compound isolated from Semen Cassiae which has multiple pharmacological activities. Nonetheless, the specific function of AO in DED is unclarified. In this study, a rodent DED model was established by benzalkonium chloride (BAC) induction, followed by topical administration of AO. The results showed that topical application of AO increased tear production, mitigated ocular surface disruption and maintained the number of goblet cells in BAC-induced DED rats (p˂0.05). ELISA revealed that AO treatment significantly (p˂0.001) reduced the production of proinflammatory cytokines and chemokines in the conjunctiva and cornea of BAC-induced DED rats. Immunohistochemical staining and western blotting showed that AO treatment suppressed the expression levels of NLR family pyrin domain containing 3 (NLRP3) inflammasome-related proteins, and inhibited activation of nuclear factor kappa B (NF-κB) signaling pathway in rat conjunctiva and cornea (p˂0.001). In conclusion, AO treatment alleviates BAC-induced DED in rats by inhibiting NF-κB/NLRP3 inflammasome signaling pathway.

Exploration the interaction of cadmium and copper toxic effects in pakchoi (Brassica chinensis L) roots through combinatorial transcriptomic and weighted gene co-expression network analysis.

The interaction between cadmium(Cd) and copper(Cu) during combined pollution can lead to more complex toxic effects on humans and plants.However, there is still a lack of sufficient understanding regarding the types of interactions at the plant molecular level and the response strategies of plants to combined pollution. To assess this, we investigated the phenotypic and transcriptomic patterns of pakchoi (Brassica chinensis L) roots in response to individual and combined pollution of Cd and Cu. The results showed that compared to single addition, the translocation factor of heavy metals in roots significantly decreased (p < 0.05) under the combined addition, resulting in higher accumulation of Cd and Cu in the roots. Transcriptomic analysis of pakchoi roots revealed that compared to single pollution, there were 312 and 1926 differentially expressed genes (DEGs) specifically regulated in the Cd2Cu20 and Cd2Cu100 combined treatments, respectively. By comparing the expression of these DEGs among different treatments, we found that the combined pollution of Cd and Cu mainly affected the transcriptome of the roots in an antagonistic manner. Enrichment analysis indicated that pakchoi roots upregulated the expression of genes involved in glucosetransferase activity, phospholipid homeostasis, proton transport, and the biosynthesis of phenylpropanoids and flavonoids to resist Cd and Cu combined pollution. Using weighted gene co-expression network analysis (WGCNA), we identified hub genes related to the accumulation of Cd and Cu in the roots, which mainly belonged to the LBD, thaumatin-like protein, ERF, MYB, WRKY, and TCP transcription factor families. This may reflect a transcription factor-driven trade-off strategy between heavy metal accumulation and growth in pakchoi roots. Additionally, compared to single metal pollution, the expression of genes related to Nramp, cation/H+ antiporters, and some belonging to the ABC transporter family in the pakchoi roots was significantly upregulated under combined pollution. This could lead to increased accumulation of Cd and Cu in the roots. These findings provide new insights into the interactions and toxic mechanisms of multiple metal combined pollution at the molecular level in plants.

Single and mixture toxicity of cadmium and copper to swim bladder in early life stages of Japanese medaka (Oryzias latipes).

Toxicity observed in aquatic ecosystems often cannot be explained by the action of a single pollutant. Likewise, evaluation standards formulated by a single effect cannot truly reflect the environmental quality requirements. The study of mixtures is needed to provide environmental relevance and knowledge of combined toxicity. In this study, the embryos of Japanese medaka (Oryzias latipes) were treated with individual and binary mixture of copper (Cu) and cadmium (Cd) until 12 days post-fertilization (dpf). Hatching, mortality, development, histology and gene expression were assessed. Our results showed that the highest concentration mixture of Cd (10 mg/L) and Cu (1 mg/L) affected survival, hatching time and hatching success. Occurrence of uninflated swim bladder was the highest (value) with exposure to 10 mg/L Cd. Swim bladder was commonly over-inflated in a mixture (0.1 mg/L Cd + 1.0 mg/L Cu) exposure. Individuals exposed to the mixture (0.1 Cd + 1.0 Cu mg/L) showed up to a 7.69% increase in swim bladder area compared to the control group. The mixtures containing 0.1 or 10 mg/L Cd, each with 1.0 mg/L Cu resulted in significantly increased of Pbx1b expression, higher than any Cd or Cu alone (p < 0.01). In the co-exposure group (0.1/10 Cd + 1.0 Cu mg/L), Pbx1b expression was found at 12 dpf but not 7 dpf in controls. Higher concentrations of Cd may progressively reduce Pbx1b expression, potentially explaining why 75% of individuals in the 10 mg/L Cd group failed to inflate their swim bladders. Additionally, the swim bladder proved to be a valuable bio-indicator for biological evaluation.

Effects of cadmium and copper mixtures on antibiotic resistance genes in rhizosphere soil.

The evolvement and development of antibiotic resistance in microorganisms may be influenced by metals; however, it is still unclear how cadmium (Cd) and copper (Cu) combined affect the distribution and presence of antibiotic-resistance genes (ARGs) in rhizosphere soil. The aims of this research were to (1) compare the distribution patterns of bacterial communities and ARGs in response to the effects of Cd and Cu both separately and combined; (2) explore the possible mechanisms underlying the variation in soil bacterial communities and ARGs in addition to the combined effects of Cd, Cu, and various environmental variables (nutrients, pH, etc.); and (3) provide a reference for assessing the risks of metals (Cd and Cu) and ARGs. The findings showed that the multidrug resistance genes acrA and acrB and the transposon gene intI-1 were present in high relative abundance in bacterial communities. Cadmium and Cu had a substantial interaction effect on the abundance of acrA, whereas Cu had a notable main effect on the abundance of intI-1. According to the network analysis, the strong links between bacterial taxa and specific ARGs revealed that most ARGs were hosted by Proteobacteria, Actinobacteria, and Bacteroidetes. According to structural equation modeling, Cd had a larger effect on ARGs than Cu. Compared to previous analyses of ARGs, bacterial community diversity had little effect on ARGs in this study. Overall, the results may have important consequences for determining the possible hazard of soil metals and extend the understanding of how Cd and Cu co-select ARGs in rhizosphere soils.

Exposure estimates of parabens from personal care products compared with biomonitoring data in human hair from Northeast China.

Parabens (PBs), a class of endocrine-disrupting chemicals (EDCs), are extensively used as additives in personal care products (PCPs); however, distinguishing between endogenous and exogenous contamination from PCPs in hair remains a challenge. We conducted a comprehensive analysis of the levels, distribution patterns, impact factors, and sources of PBs in 119 human hair samples collected from Changchun, northeast China. The detection rates of methylparaben (MeP), propylparaben (PrP), and ethylparaben (EtP) in hair samples were found to be 100%. The concentration of PBs in hair followed the order of MeP (57.48 ng/g) > PrP (46.40 ng/g) > EtP (6.80 ng/g). The concentration of PrP in female hair was significantly higher (65.38 ng/g) than that observed in male hair (7.82 ng/g) (p < 0.05). The levels of excretion rates of MeP (ERMeP) and excretion rates of PrP (ERPrP) in the hair-dying samples (ERMeP: 17.89 ng/day; ERPrP: 14.15 ng/day) were found to be 2.52 and 2.40 times higher, respectively, compared to the non-hair-dying samples (ERMeP: 7.09 ng/day; ERPrP: 6.05 ng/day). However, the system exposure dosage (SED) results revealed that although hair dyes exhibited higher PBs, human exposure was found to be lower than certain PCPs. The results of the correlation analysis revealed that toner, face cream, body lotion, and hair conditioner were identified as the primary sources of PBs in male hair. Furthermore, the human exposure resulting from the utilization of female hair dye and serum exhibited a positive correlation with hair ERMeP and ERPrP levels, indicating in the screening of samples, excluding hair samples using hair dye and haircare essential oil can effectively avoid the interference caused by exogenous contamination from PCPs.

Developmental Neurotoxicity of Trichlorfon in Zebrafish Larvae.

Trichlorfon is an organophosphorus pesticide widely used in aquaculture and has potential neurotoxicity, but the underlying mechanism remains unclear. In the present study, zebrafish embryos were exposed to trichlorfon at concentrations (0, 0.1, 2 and 5 mg/L) used in aquaculture from 2 to 144 h post fertilization. Trichlorfon exposure reduced the survival rate, hatching rate, heartbeat and body length and increased the malformation rate of zebrafish larvae. The locomotor activity of larvae was significantly reduced. The results of molecular docking revealed that trichlorfon could bind to acetylcholinesterase (AChE). Furthermore, trichlorfon significantly inhibited AChE activity, accompanied by decreased acetylcholine, dopamine and serotonin content in larvae. The transcription patterns of genes related to acetylcholine (e.g., ache, chrna7, chata, hact and vacht), dopamine (e.g., drd4a and drd4b) and serotonin systems (e.g., tph1, tph2, tphr, serta, sertb, htrlaa and htrlab) were consistent with the changes in acetylcholine, dopamine, serotonin content and AChE activity. The genes related to the central nervous system (CNS) (e.g., a1-tubulin, mbp, syn2a, shha and gap-43) were downregulated. Our results indicate that the developmental neurotoxicity of trichlorfon might be attributed to disorders of cholinergic, dopaminergic and serotonergic signaling and the development of the CNS.

Characteristics and health risks of population exposure to phthalates via the use of face towels.

The production of face towels is growing at an annual rate of about 4% in China, reaching 1.13 million tons by 2021. Phthalates (PAEs) are widely used in textiles, and face towels, as an important household textile, may expose people to PAEs via the skin, further leading to health risks. We collected new face towels and analyzed the distribution characterization of PAEs in them. The changes of PAEs were explored in a face towel use experiment and a simulated laundry experiment. Based on the use of face towels by 24 volunteers, we calculated the estimated daily intake (EDI) and comprehensively assessed the hazard quotient (HQ), hazard index (HI), and dermal cancer risk (DCR) of PAEs exposure in the population. PAEs were present in new face towels at total concentrations of

Efficient extraction and antioxidant activity of polyphenols from Antrodia cinnamomea.

BACKGROUND: Antrodia cinnamomea, a rare medicinal fungus, has been increasingly studied in recent years because of its abundant secondary metabolites which are beneficial to humans. However, there is a lack of research on its polyphenols which are of good research value due to their antioxidant, anti-inflammatory, hypoglycemic and other activities. RESULTS: In this study, the effects of different extraction conditions on the yield of its polyphenols were investigated. Deep-Eutectic Solvents composed of choline chloride and malonic acid had the best extraction efficiency, with the optimal extraction conditions being as follows: a solid-liquid ratio of 40 mg/mL, an extraction temperature of 55 °C, an extraction time of 70 min and a DES with 20% water content. Under these conditions, the extraction yield of polyphenols reached 22.09 mg/g which was about 2 times that of alcohol-based extraction (10.95 mg/g). In vitro antioxidant test results further showed that polyphenols from A. cinnamomea had strong antioxidant activities. When the concentration of polyphenols reached 0.1 mg/mL of polyphenols, the scavenging activity of free radical basically reached its maximum, with values of 94.10%, 83.34% and 95.42% for DPPH, ABTS+ and ·OH scavenging. In this case, the corresponding IC50 values were 0.01, 0.014 and 0.007 mg/mL, respectively. CONCLUSIONS: This study lays the foundation for the efficient extraction and application of polyphenols from A. cinnamomea.

Transposon insertions within alleles of BnaFT.A2 are associated with seasonal crop type in rapeseed.

KEY MESSAGE: We identified two new transposon insertions within the promoter of BnaFT.A2 in addition to an existing 288 bp MITE within the second intron. Each insertion event corresponds to a distinct BnaFT.A2 haplotype and is closely associated with established crop seasonal ecotypes. Florigen, encoded by FLOWERING LOCUS T (FT), plays key roles not only as a flowering hormone, but also a universal growth factor affecting several aspects of plant architecture. In rapeseed, BnaFT.A2 has been revealed as one of the major loci associated with flowering time and different ecotypes. However, it is unclear how allelic variations of BnaFT.A2 affect its function in flowering time regulation and beyond. In this study, we confirmed an existing 288 bp miniature inverted-repeat transposable element (MITE) insertion within the second intron and identified two new insertions within the promoter of BnaFT.A2-a 3971 bp CACTA and a 1079 bp Helitron. Each insertion event corresponds to a distinct BnaFT.A2 haplotype and is closely associated with established crop seasonal ecotypes. These alleles have similar tissue-specific expression patterns but discrete transcriptional patterns tightly associated with rapeseed flowering time and ecotype. RNAi lines and mutants of BnaFT.A2 flowered significantly later than controls. Differentially expressed genes (DEGs), identified in transcriptomic profiling of seedling leaves from two loss-of-function mutants (Bnaft.a2-L1 and Bnaft.a2-L2) compared with controls, indicated significant enrichment for hormone metabolic genes and roles related to plant cell wall synthesis and photosynthesis. Plants with loss-of-function BnaFT.A2 had smaller leaves and lower net photosynthetic rate compared to controls. These findings not only further clarify the genetic basis of flowering time variation and ecotype formation in B. napus, but also provide an additional toolbox for genetic improvement of seasonal adaptation and production.

Association between mitochondrial DNA methylation and internal exposure to polycyclic aromatic hydrocarbons (PAHs), nitrated-PAHs (NPAHs) and oxygenated-PAHs (OPAHs) in young adults from Tianjin, China.

Polycyclic aromatic hydrocarbons (PAHs), nitrated-PAHs (NPAHs) and oxygenated-PAHs (OPAHs) are environmental pollutants with adverse effects on human health. The correlation between the concentrations of PAHs, NPAHs and OPAHs in human plasma and the methylation level of mitochondrial DNA (mtDNA) was investigated using data from 110 plasma samples collected in Tianjin, China. The median concentrations of PAHs, NPAHs and OPAHs were 16.0 (IQR: 14.4-20.7) ng/mL, 82.2 (IQR: 63.1-97.6) ng/mL and 49.6 (IQR: 28.6-53.8) ng/mL, and the mean proportions were 13.4%, 56.5% and 30.1%, respectively. Bisulfite-PCR pyrosequencing was used to measure the methylation level of MT-CO1 and tRNA-Leu. The methylation levels of two mitochondrial genes (MT-CO1, tRNA-Leu) including four CpG sites (MT-CO1-P1, MT-CO1-P2, tRNA-Leu-P1 and tRNA-Leu-P2) were 0.67% ± 1.38%, 13.54% ± 2.59%, 7.23% ± 5.35% and 1.64% ± 2.94%, respectively. To the best of our knowledge, this is the first time that significant correlations were found between PAHs and their derivatives exposure and mtDNA methylation levels.

The effect of carbonization temperature on the capacity and mechanisms of Cd(II)-Pb(II) mix-ions adsorption by wood ear mushroom sticks derived biochar.

Heavy metals often coexist in contaminated environmental media, and competition between heavy metals for adsorption sites influences the absorption capacity of biochar. In this study, the adsorption mechanism of pyrolytically modified wood ear mushroom sticks (250, 450, and 650 °C) as a new bio-adsorbent for single-ion and mixed-ion solutions Cd2+ and Pb2+ Biochar adsorption experiments showed that the adsorption abilities of Cd2+ and Pb2+ increased with increasing WMBC (wood ear mushroom sticks biochar) pyrolysis temperature. According to the Langmuir model, the maximum adsorption capacity of Cd2+ and Pb2+increased with higher pyrolysis temperature, being 29.84, 39.08, 46.16 mg·g-1and 124.3, 186.8, 234.2 mg·g-1, respectively for three different pyrolysis temperatures 250, 450, and 650 °C. WMBC exhibited a stronger adsorption ability for Pb2+ than for Cd2+. Competition between the two heavy metals severely inhibited the adsorption of Cd2+. Based on X-ray diffraction (XRD), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS), and Fourier transform infrared spectroscopy (FTIR) analyses, the dominant interaction mechanisms were determined to be complexation, ion exchange, precipitation, and C-π interaction. The results suggest WMBC shows promise as a novel, cheap, and effective adsorbent that can be used to remove both Cd2+ and Pb2+ pollutants from environmental media.

A novel homozygous missense mutation in AK7 causes multiple morphological anomalies of the flagella and oligoasthenoteratozoospermia.

PURPOSE: To identify the genetic causes of multiple morphological anomalies of the flagella (MMAF) and oligoasthenoteratozoospermia (OAT). METHODS: Whole-exome sequencing (WES) was performed on the proband to identify pathogenic mutation for infertility. Western blotting and immunofluorescence analysis detected the expression level and localization of adenylate kinase 7 (AK7). RESULTS: We identified a novel homozygous missense mutation (NM_152327: c.1846G > A; p.E616K) in AK7 in two brothers with MMAF and OAT from a consanguineous family by WES. Western blotting and immunofluorescence experiments determined that the expression level of AK7 decreased in the sperm from the proband. The proband and his wife underwent two cycles of intracytoplasmic sperm injection (ICSI) treatment but got unfavorable outcomes. CONCLUSION: This study could provide precise genetic diagnosis for the patient and expand the spectrum of AK7 mutations.

Coordinated Positioning Method for Shortwave Anti-Multipath Based on Bayesian Estimation.

Coordinated positioning based on direction of arrival (DOA)-time difference of arrival (TDOA) is a research area of great interest in beyond-visual-range target positioning with shortwave. The DOA estimation accuracy greatly affects the accuracy of coordinated positioning. With existing positioning methods, the elevation angle's estimation accuracy in multipath propagation decreases sharply. Accordingly, the positioning accuracy also decreases. In this paper, the elevation angle is modeled as a random variable, with its probability distribution reflecting the characteristics of multipath propagation. A new coordinated positioning method based on DOA-TDOA and Bayesian estimation with shortwave anti-multipath is proposed. First, a convolutional neural network is used to learn the three-dimensional spatial spectrogram to make an intelligent decision on the number of single and multiple paths, and to obtain a probability distribution of the elevation angle under multiple paths. Second, the elevation angle's estimated value is modified using the elevation angle's probability distribution. The modified elevation angle's estimated value is substituted into a DOA pseudo-linear observation equation, and the target position's estimated value is obtained using the matrix QR decomposition iteration algorithm. Finally, a TDOA pseudo-linear observation equation is established using the target estimate obtained in the DOA stage, and the coordinated positioning result is obtained using the matrix QR decomposition iteration algorithm again. Simulation results demonstrated that the proposed method had a stronger anti-multipath capability than traditional methods, and it improved the coordinated positioning accuracy of the DOA and TDOA. Measured data were used to validate the proposed method.

Precision 3D printed meniscus scaffolds to facilitate hMSCs proliferation and chondrogenic differentiation for tissue regeneration.

BACKGROUND: The poor regenerative capability and structural complexity make the reconstruction of meniscus particularly challenging in clinic. 3D printing of polymer scaffolds holds the promise of precisely constructing complex tissue architecture, however the resultant scaffolds usually lack of sufficient bioactivity to effectively generate new tissue. RESULTS: Herein, 3D printing-based strategy via the cryo-printing technology was employed to fabricate customized polyurethane (PU) porous scaffolds that mimic native meniscus. In order to enhance scaffold bioactivity for human mesenchymal stem cells (hMSCs) culture, scaffold surface modification through the physical absorption of collagen I and fibronectin (FN) were investigated by cell live/dead staining and cell viability assays. The results indicated that coating with fibronectin outperformed coating with collagen I in promoting multiple-aspect stem cell functions, and fibronectin favors long-term culture required for chondrogenesis on scaffolds. In situ chondrogenic differentiation of hMSCs resulted in a time-dependent upregulation of SOX9 and extracellular matrix (ECM) assessed by qRT-PCR analysis, and enhanced deposition of collagen II and aggrecan confirmed by immunostaining and western blot analysis. Gene expression data also revealed 3D porous scaffolds coupled with surface functionalization greatly facilitated chondrogenesis of hMSCs. In addition, the subcutaneous implantation of 3D porous PU scaffolds on SD rats did not induce local inflammation and integrated well with surrounding tissues, suggesting good in vivo biocompatibility. CONCLUSIONS: Overall, this study presents an approach to fabricate biocompatible meniscus constructs that not only recapitulate the architecture and mechanical property of native meniscus, but also have desired bioactivity for hMSCs culture and cartilage regeneration. The generated 3D meniscus-mimicking scaffolds incorporated with hMSCs offer great promise in tissue engineering strategies for meniscus regeneration.

Potential health risks of metals in skin care products used by Chinese consumers aged 19-29 years.

Metal contamination of skin care products that occurs during their production poses potential health risks, which are of increasing concern, to consumers. Here, we collected 570 responses to an online survey to analyze the usage pattern of skin care products across China. Then a total of 30 commonly used skin care products with various prices and applications were purchased. The concentrations of metals (Al, Zn, Cu, Ni, Cr, Pb, Hg, and Cd) and metalloid As, were determined. Next, we improved the frequency calculation method and used the weighted exposure frequency to calculate the dermal absorption dose (DAD). The amounts of Zn, Cr, and Al that were assimilated by the human body via uptake were approximately 2 orders of magnitude greater than those of Pb, Hg, Cd, Ni and metalloid As. In addition, younger consumers were at higher risk of metals exposure than older consumers because of their higher frequency of use of skin care products. Al and Zn posed higher risk to consumers because of its high DAD. There was no significant chronic non-carcinogenic health risk (hazard index < 1) posed by skincare product use.

Pathogenesis of acephalic spermatozoa syndrome caused by splicing mutation and de novo deletion in TSGA10.

PURPOSE: To identify the genetic causes for acephalic spermatozoa syndrome. METHODS: Whole-exome sequencing was performed on the proband from a non-consanguineous to identify pathogenic mutations for acephalic spermatozoa syndrome. Quantitative real-time polymerase chain reaction and whole genome sequencing were subjected to detect deletion. The functional effect of the identified splicing mutation was investigated by minigene assay. Western blot and immunofluorescence were performed to detect the expression level and localization of mutant TSGA10 protein. RESULTS: Here, we identified a novel heterozygous splicing mutation in TSGA10 (NM_025244: c.1108-1G > T), while we confirmed that there was a de novo large deletion in the proband. The splicing mutation led to the skipping of the exon15 of TSGA10, which resulted in a truncated protein (p. A370Efs*293). Therefore, we speculated that the splicing mutation might affect transcription and translation without the dosage compensation of a normal allele, which possesses a large deletion including intact TSGA10. Western blot and immunofluorescence demonstrated that the very low expression level of truncated TSGA10 protein led the proband to present the acephalic spermatozoa phenotype. CONCLUSION: Our finding expands the spectrum of pathogenic TSGA10 mutations that are responsible for ASS and male infertility. It is also important to remind us of paying attention to the compound heterozygous deletion in patients from non-consanguineous families, so that we can provide more precise genetic counseling for patients.

Optimization of Extraction Process and the Antioxidant Activity of Phenolics from Sanghuangporus baumii.

Sanghuangporus baumii, is a widely used medicinal fungus. The polyphenols extracted from this fungus exert antioxidant, anti-inflammatory, and hypoglycemic effects. In this study, polyphenols from the fruiting bodies of S. baumii were obtained using the deep eutectic solvent (DES) extraction method. The factors affecting the extraction yield were investigated at different conditions. Based on the results from single-factor experiments, response surface methodology was used to optimize the extraction conditions. The scavenging ability of the polyphenols on •OH, DPPH, and ABTS+ was determined. The results showed that the DES system composed of choline chloride and malic acid had the best extraction yield (6.37 mg/g). The optimal extraction parameters for response surface methodology were as follows: 42 min, 58 ℃, 1:34 solid-liquid (mg/mL), and water content of 39%. Under these conditions, the yield of polyphenols was the highest (12.58 mg/g). At 0.30 mg/mL, the scavenging ability of the polyphenols on •OH, DPPH, and ABTS+ was 95.71%, 91.08%, and 85.52%, respectively. Thus, the method using DES was more effective than the conventional method of extracting phenolic compounds from the fruiting bodies of S. baumii. Moreover, the extracted polyphenols exhibited potent antioxidant activity.