Joint developmental trajectories of depression and post-traumatic stress disorder symptoms among Chinese children during COVID-19.

BACKGROUND: In early 2020, Chinese children started to demonstrate severe depression and post-traumatic stress disorder symptoms (PTSS) caused by lockdown and self-isolation (measures taken at the beginning of the COVID-19 pandemic). OBJECTIVES: Concerning the significant impact of the pandemic on children's physical and mental development, the study aimed to explore children's depression and PTSS during the COVID-19 pandemic and the protective effects of family resilience on the trajectories. METHODS: 883 children participated and completed three waves of online follow-up questionnaires. The latent growth mixture modeling (LGMM) analysis was used to explore the trajectories of children's depression and PTSS based on the individual approach. RESULTS: Two types of depression trajectories were identified and defined as the resilient group (83.01 %) and the recovery group (16.99 %); Two types of PTSS trajectories were identified and defined as the resilient group (71.12 %) and the recovery group (28.88 %); Two types of the joint trajectories of depression and PTSS were identified and defined as the resilient group (83.47 %) and the chronic group (16.53 %). The results indicated that maintaining a positive outlook (a dimension of family resilience) was the potential predictor of PTSS trajectories. CONCLUSION: The trajectories of depression and PTSS among Chinese children during the COVID-19 pandemic were heterogeneous, and there were similar evolving subtypes. Family resilience could be a critical protective factor for children and families.

Longitudinal Association Between Posttraumatic Stress Symptoms and Depression Symptoms Among Chinese Adolescents During COVID-19: Evidence from Network Perspective.

Although there are an increasing number of studies that have explored the mental health consequences of COVID-19 focusing on revealing risk factors, the longitudinal research examining the potential mechanism of the co-occurrence of posttraumatic stress symptoms (PTSS) and depression symptoms among adolescents were scarce. The present study identified the important comorbidity symptoms and explored longitudinal relationship of PTSS and depression symptoms from the network perspective. A two-wave investigation (4 months interval; T1 and T2) was conducted with a sample of 1225 Chinese adolescents. Cross-sectional network and cross-lagged panel network (CLPN) analyses were adopted. Results showed that comorbidity symptoms consisted of both overlapping and non-overlapping symptoms, including "Future foreshortening" at T1 and T2 from PTSS, and "Hard to get started" at T1 and "Not sleep well" at T2 from depression symptoms. Strong longitudinal pathways appeared from all PTSS to depression symptoms, among which the pathway from "Difficulty concentrating" to "Hard to get started" was the strongest. These findings suggest that the possible comorbidity between PTSS and depression symptoms is caused by their independent and related structures, and their longitudinal association. Clinical intervention for these symptoms may alleviate adolescents' psychological problems in the aftermath of traumatic events.

The dyadic effects of individual resilience on family resilience among Chinese parents and children during COVID-19.

Previous studies have mainly focused on examining families' struggles during the adaptive process of adversity, while the strength of family and how it arises were neglected. This study aims to explore the relationships between individual and family resilience among parents and children in families during COVID-19. Guided by the longitudinal actor-partner interdependence model, one parent and a child in 136 Chinese families completed assessments of pandemic media exposure and individual resilience in mid-February 2020 and family resilience in early March. Results showed that the child's individual resilience was positively associated with their own and their parents' family resilience, while parents' resilience was only positively associated with their own. The evidence indicated that a child's individual resilience was critical for all core family members' perceived family resilience and provided implications for family intervention programs.

Resilience Mediates the Relationship Between Parental Attachment and Posttraumatic Growth in Adolescents: A Longitudinal Study.

OBJECTIVE: Previous studies have shown that parental attachment was associated with higher levels of posttraumatic growth (PTG) in individuals who have experienced traumatic events. The aim of the current longitudinal study is to investigate resilience as one pathway through which parental attachment is related to PTG among Chinese adolescents following the Yancheng tornado. METHODS: A total of 351 adolescent survivors participated in this longitudinal study. Participants completed the revised version of Inventory of Parent and Peer Attachment (IPPA-R) at 12 months (T1), and the revised Chinese version of the Post-Traumatic Growth Inventory (PTGI-R) and the Connor and Davidson's Resilience Scale (CD-RISC) at 18 months (T2) after the tornado, respectively. RESULTS: It indicated that parental attachment at T1 has direct and positive effect on PTG at T2, and resilience at T2 fully mediated the relationship between parental attachment at T1 and PTG at T2. CONCLUSION: The findings revealed that parental attachment and resilience are two key resources that promote adolescent's PTG, and parental attachment acts through resilience to promote PTG in adolescents.

Heavy metals in daily meals and food ingredients in the Yangtze River Delta and their probabilistic health risk assessment.

Heavy metal exposure via food consumption is inadequately investigated and deserves considerable attention. We collected hundreds of food ingredients and daily meals and assessed their probabilistic health risk using a Monte Carlo simulation based on an ingestion rate investigation. The detected concentrations of four heavy metals (Cr, Cd, Pb, and Hg) in all daily meal samples were within the limits stipulated in the National Food Safety Standard (GB 2762-2017), while that for As level was excessive in 0.3 % of daily meal samples. The same results were also observed in most food ingredient samples, and a standard-exceeding ratio of 23 % of As was observed in aquatic food or products, especially seafood, which was with the highest concentration reaching 1.24 mg/kg. Combining the detected heavy metal amounts with the ingestion rate investigation, the hazard quotients (HQs) of As, Cr, Cd, Pb, and Hg in daily meals and food ingredients were all calculated as lower than 1 (no obvious harm), while the incremental lifetime cancer risk (ILCR) of As and Cr (>1 × 10-4), indicating that the residual As posed potential health effects to human health. It was noteworthy that the proportion of aquatic foods only accounted for 6.3 % of daily meals, but they occupied 41.1 % of the heavy metal exposure, which could be attributed to the high amounts of heavy metals in aquatic foods. This study not only provided basic data of heavy metal exposure and potential health risks through daily oral dietary intake, but also illuminated the contribution of different kinds of food ingredients. Specifically, the study highlighted the contamination of aquatic foods with As, especially seafood such as shellfish and bivalves.

Effect of oridonin in reversing cisplatin resistance in melanoma cells and its mechanism / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨冬凌草甲素（Ori）逆转人黑色素瘤细胞顺铂（DDP）耐药的作用及其机制。方法：分别将黑色素瘤DDP耐药细胞A375/DDP和M14/DDP分为对照组、2 μmol/L Ori组、4 mg/L DDP组和2 μmol/L Ori+4 mg/L DDP组。CCK-8法、Transwell实验、Annexin Ⅴ-FITC/PI染色流式细胞术分别检测各组细胞的增殖活力、侵袭和迁移能力及凋亡水平，透射电子显微镜观察自噬小体，免疫荧光染色法观察微管相关蛋白轻链3（LC3）点状结构，WB法检测A375/DDP细胞自噬相关蛋白Beclin-1、p62、LC3Ⅱ和LC3Ⅰ的表达。结果: 与4 mg/L DDP组相比，2 μmol/L Ori+4 mg/L DDP组细胞增殖活力、迁移和侵袭能力均显著下降（均P<0.01），凋亡水平显著升高（P<0.01）。4 mg/L DDP组细胞中可见大量自噬小体以及LC3点状染色，但2 μmol/L Ori+4 mg/L DDP组仅可见少量。与对照组相比，4 mg/L DDP组细胞中Beclin-1和LC3Ⅱ/LC3Ⅰ的蛋白表达水平均显著升高（均P<0.01），p62的蛋白表达水平显著降低（P<0.05或P<0.01）；与4 mg/L DDP组相比，2 μmol/L Ori+4 mg/L DDP组细胞中Beclin-1和LC3Ⅱ/LC3Ⅰ的表达水平均显著降低（均P<0.01），p62的表达水平显著升高（P<0.05）。结论: Ori可增加耐药黑色素瘤细胞对DDP的敏感性，此作用可能与其抑制DDP引起的细胞自噬有关。

Curcumol Synergizes with Cisplatin in Osteosarcoma by Inhibiting M2-like Polarization of Tumor-Associated Macrophages.

Osteosarcoma is the most prevalent bone cancer, and chemotherapy is still an indispensable treatment in its clinical practice. Cisplatin (CDDP) has become the most commonly used agent for osteosarcoma, although the outcomes of CDDP chemotherapy remain unsatisfactory because of frequent resistance. Here, we report on a promising combination therapy where curcumol, a bioactive sesquiterpenoid, enhanced CDDP-induced apoptosis to eradicate osteosarcoma cells, and revealed that M2-like macrophages might be the underlying associated mechanisms. First, we observed that curcumol enhanced the CDDP-mediated inhibition of cell proliferation and augmented the apoptosis in osteosarcoma cell lines. Curcumol contributed to preventing the migration of osteosarcoma cells when combined with CDDP. Moreover, this drug combination showed more potent tumor-growth suppression in the orthotopic transplantation of osteosarcoma K7M2 WT cells. We then estimated chemotherapy-associated drug-resistant genes, including ABCB1, ABCC1 and ABCG2, and found that curcumol significantly reversed the mRNA levels of CDDP-induced ABCB1, ABCC1 and ABCG2 genes in the tumor tissue. Moreover, M2-like macrophages were enriched in osteosarcoma tissues, and were largely decreased after curcumol and CDDP treatment. Taken together, these findings suggest that curcumol inhibits the polarization of M2-like macrophages and could be a promising combination strategy to synergize with CDDP in the osteosarcoma.

An Expedient Total Synthesis of Chivosazole†F: an Actin-Binding Antimitotic Macrolide from the Myxobacterium Sorangium Cellulosum.

A unified strategy for the chemical synthesis of the chivosazoles is described. This strategy is based on two closely related approaches involving the late-stage installation of the isomerization-prone (2Z,4E,6Z,8E)-tetraenoate motif, and an expedient fragment-assembly procedure. The result is a highly convergent total synthesis of chivosazole F through the orchestration of three mild Pd/Cu-mediated Stille cross-coupling reactions, including the use of a one-pot, site-selective, three-component process, in combination with controlled installation of the requisite alkene geometry.

Protrusion-localized STAT3 mRNA promotes metastasis of highly metastatic hepatocellular carcinoma cells in vitro.

AIM: Recent evidence shows that localization of mRNAs and their protein products at cellular protrusions plays a decisive function in the metastasis of cancer cells. The aim of this study was to identify the variety of proteins encoded by protrusion-localized mRNAs and their roles in the metastasis and invasion of liver cancer cells. METHODS: Highly metastatic hepatocellular carcinoma cell line HCCLM3 and non-metastatic hepatocellular carcinoma cell line SMMC-7721 were examined. Cell protrusions (Ps) were separated from cell bodies (CB) using a Boyden chamber assay; total mRNA population in CB and Ps fractions was analyzed using high-throughput direct RNA sequencing. The localization of STAT3 mRNA and protein at Ps was confirmed using RT-qPCR, RNA FISH, and immunofluorescence assays. Cell migration capacity and invasiveness of HCCLM3 cells were evaluated using MTT, wound healing migration and in vitro invasion assays. The interaction between Stat3 and growth factor receptors was explored with co-immunoprecipitation assays. RESULTS: In HCCLM3 cells, 793 mRNAs were identified as being localized in the Ps fraction according to a cut-off value (Ps/CB ratio) >1.6. The Ps-localized mRNAs could be divided into 4 functional groups, and were all closely related to the invasive and metastatic properties. STAT3 mRNA accumulated in the Ps of HCCLM3 cells compared with non-metastatic SMMC-7721 cells. Treatment of HCCLM3 cells with siRNAs against STAT3 mRNA drastically decreased the cell migration and invasion. Moreover, Ps-localized Stat3 was found to interact with pseudopod-enriched platelet-derived growth factor receptor tyrosine kinase (PDGFRTK) in a growth factor-dependent manner. CONCLUSION: This study reveals STAT3 mRNA localization at the Ps of metastatic hepatocellular carcinoma HCCLM3 cells by combining application of genome-wide and gene specific description and functional analysis.

Theoretical study on the acidities of chiral phosphoric acids in dimethyl sulfoxide: hints for organocatalysis.

The pKa values of 41 chiral phosphoric acid-family catalysts in DMSO were predicted using the SMD/M06-2x/6-311++G(2df,2p)//B3LYP/6-31+G(d) method for the first time. The study showed that the calculated pKa's range from -4.23 to 6.16 for absolute pKa values and from -4.21 to 6.38 for relative pKa values. Excellent agreement between the calculated and experimental pKa's was achieved for the few available cases (to a precision of around 0.4 pKa unit), indicating that this strategy may be suitable for calculating highly accurate pKa's. A good linear correlation between the pKa's for 3 and 3' disubstituted phenyl BINOL phosphoric acids and the Hammett constants was obtained. The relationship between the acidities of phosphoric acid catalysts and their reaction activity and selectivity was also discussed. Knowledge of the pKa values of phosphoric acids should be of great value for the understanding of chiral Brønsted acid-catalyzed reactions and may aid in future catalyst design.

Synthesis of optically enriched spirocyclic benzofuran-2-ones by bifunctional thiourea-base catalyzed double-Michael addition of benzofuran-2-ones to dienones.

A highly enantioselective catalytic double-Michael addition reaction of substituted benzofuran-2-ones with divinyl ketones promoted by readily accessible tertiary amine-thiourea Cinchona alkaloids has been developed. A number of optically enriched spirocyclic benzofuran-2-ones were prepared in very good yields (up to 99 %), diastereoselectivities (up to 19:1 d.r.), and very good enantioselectivities (up to 92 % ee). Density functional theory (DFT) calculations were performed to investigate the origin of stereoselectivity.

Phylogenetic analysis reveals the evolution and diversification of cyclins in eukaryotes.

Cyclins are a family of diverse proteins that play fundamental roles in regulating cell cycle progression in Eukaryotes. Cyclins have been identified from protists to higher Eukaryotes, while its evolution remains vague and the findings turn out controversial. Current classification of cyclins is mainly based on their functions, which may not be appropriate for the systematic evolutionary analysis. In this work, we performed comparative and phylogenetic analysis of cyclins to investigate their classification, origin and evolution. Cyclins originated in early Eukaryotes and evolved from protists to plants, fungi and animals. Based on the phylogenetic tree, cyclins can be divided into three major groups designated as the group I, II and III with different functions and features. Group I plays key roles in cell cycle, group II varied in actions are kingdom (plant, fungi and animal) specific, and group III functions in transcription regulation. Our results showed that the dominating cyclins (group I) diverged from protists to plants, fungi and animals, while divergence of the other cyclins (groups II and III) has occurred in protists. We also discussed the evolutionary relationships between cyclins and cyclin-dependent kinases (CDKs) and found that the cyclins have undergone divergence in protists before the divergence of animal CDKs. This reclassification and evolutionary analysis of cyclins might facilitate understanding eukaryotic cell cycle control.

Asymmetric Michael addition reactions of 3-substituted benzofuran-2(3H)-ones to nitroolefins catalyzed by a bifunctional tertiary-amine thiourea.

The current work reports an organocatalytic strategy for the asymmetric catalysis of chiral benzofuran-2(3H)-ones bearing 3-position all-carbon quaternary stereocenters. Accordingly, highly enantioselective Michael addition reactions of 3-substituted benzofuran-2(3H)-ones to nitroolefins have been developed by utilizing a bifunctional tertiary-amine thiourea catalyst. The reactions accommodate a number of nitroolefins and 3-substituted benzofuran-2(3H)-ones to give the desired chiral benzofuran-2(3H)-one products with moderate to excellent yields (up to 98%) and moderate to very good selectivities (up to 19 : 1 dr and up to 91% ee). Theoretical calculations using the DFT method on the origin of the stereoselectivity were conducted. The effect of the nitroolefin substituent position on the stereoselectivity of the Michael addition reaction was also theoretically rationalized.

Chiral biscinchona alkaloid promoted asymmetric allylic alkylation of 3-substituted benzofuran-2(3H)-ones with Morita-Baylis-Hillman carbonates.

A highly diastereo- and enantioselective asymmetric allylic alkylation reaction with respect to prochiral 3-substituted benzofuran-2(3H)-ones and MBH carbonate by a chiral biscinchona alkaloid catalyst was investigated. The corresponding adducts, containing a quaternary center at the C3-position of the benzofuran-2(3H)-one as well as a vicinal tertiary center, were generally obtained in high yields (up to 97%) with very good diastereo- (up to 98:2 dr) and enantioselectivities (up to 95% ee).

PTD4-apoptin protein and dacarbazine show a synergistic antitumor effect on B16-F1 melanoma in vitro and in vivo.

PTD4-apoptin protein enters cells and harbors tumor-selective cell death activity. Dacarbazine is the mainstay of treatment for malignant melanoma. In this study, we investigated the cytotoxic effect of PTD4-apoptin protein and/or dacarbazine in mouse B16-F1 and human A875 and SK-MEL-5 melanoma cells in vitro and by means of a mouse B16-F1 melanoma model in vivo. PTD4-apoptin protein inhibits the growth of B16-F1, A875 and SK-MEL-5 melanoma cells in a dose-dependent manner, but not in normal human cell lines WI-38 and L-02. PTD4-apoptin combined with dacarbazine revealed a synergistic cytotoxic effect (coefficient of drug interaction<1) in all three different tumor cell lines. In vivo, PTD4-apoptin protein and dacarbazine alone effectively inhibited the growth of B16-F1 melanoma in C57BL/6 mice. Strikingly, combined PTD4-apoptin/dacarbazine treatment significantly increased the antitumor effect in comparison to the single treatments. As important, a combined PTD4-apoptin/dacarbazine treatment with a 50% reduction of dacarbazine revealed similar antitumor activities, without detectable hematologic side effects. A combined PTD4-apoptin/dacarbazine treatment represents a promising novel efficient and safe anticancer strategy.