COVID-19 pandemic amplified mortality rates among adolescents with bipolar disorder through family-related factors.

BACKGROUND: Recently, a growing number of adolescents have been afflicted with mental disorders, with annual morbidity rates on the rise. This trend has been exacerbated by the global coronavirus disease 2019 (COVID-19) pandemic, leading to a surge in suicide and self-harm rates among this demographic. AIM: To investigate the impact of the COVID-19 pandemic on adolescent bipolar disorder (BD), along with the underlying factors contributing to heightened rates of suicide and self-harm among adolescents. METHODS: A comprehensive statistical analysis was conducted utilizing clinical interviews and self-reports obtained from patients or their guardians. Diagnostic criteria for BDs were based on the Diagnostic and statistical manual of mental disorders, international classification of diseases-11, and the National institute of mental health research domain criteria. Statistical analyses were performed using SPSS 26.0 software, with significance set at P < 0.05. RESULTS: A cohort of 171 adolescents diagnosed with BD between January 1, 2018, and December 31, 2022, was included in the analysis. The gender distribution was 2.8:1 (female to male), with ages ranging from 11 to 18 years old. Major factors contributing to adolescent BDs included familial influences, academic stress, genetic predisposition and exposure to school-related violence. Notably, a significant increase in suicide attempts and self-harm incidents was observed among adolescents with BD during the COVID-19 pandemic. Statistical analysis indicated that the pandemic exacerbated familial discord and heightened academic stress, thereby amplifying the prevalence of suicidal behavior and self-harm among adolescents. CONCLUSION: The COVID-19 pandemic has exacerbated familial tensions and intensified the incidence of suicide and self-harm among adolescents diagnosed with BD. This study underscores the urgent need for societal, familial and educational support systems to prioritize the well-being of adolescents and offers valuable insights and guidelines for the prevention, diagnosis and treatment of adolescent BDs.

Gene delivery to breast cancer by incorporated EpCAM targeted DARPins into AAV2.

OBJECTIVE: The aim of this study is to evaluate an AAV vector that can selectively target breast cancer cells and to investigate its specificity and anti-tumor effects on breast cancer cells both in vitro and in vivo, offering a new therapeutic approach for the treatment of EpCAM-positive breast cancer. METHODS: In this study, a modified AAV2 viral vector was used, in which EpCAM-specific DARPin EC1 was fused to the VP2 protein of AAV2, creating a viral vector that can target breast cancer cells. The targeting ability and anti-tumor effects of this viral vector were evaluated through in vitro and in vivo experiments. RESULTS: The experimental results showed that the AAV2MEC1 virus could specifically infect EpCAM-positive breast cancer cells and accurately deliver the suicide gene HSV-TK to tumor tissue in mice, significantly inhibiting tumor growth. Compared to the traditional AAV2 viral vector, the AAV2MEC1 virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth. CONCLUSION: This study demonstrates that AAV2MEC1 is a gene delivery vector capable of targeting breast cancer cells and achieving selective targeting in mice. The findings offer a potential gene delivery system and strategies for gene therapy targeting EpCAM-positive breast cancer and other tumor types.

[Effects of a novel spermine oxidase inhibitor SI-4650 on proliferation and EMT of human ovarian cancer SKVO-3 cells].

Objective: To investigate the effects of SI-4650, a novel small molecule inhibitor of spermine oxidase (SMO), on the proliferation and epithelial mesenchymal transformation (EMT) of human ovarian cancer SKVO-3 cells as well as its underlying molecular mechanisms. Methods: SKVO-3 cells treated with 0 µmol/L SI-4650 were used as control group, SKVO-3 cells treated with 30, 60 µmol/L SI-4650 were used as experimental group. The effects of SI-4650 on the activity of SMO, the polyamine contents and the cellular reactive oxygen species (ROS) were detected. Cell proliferation, cell cycle and mitochondrial membrane potential change of SKVO-3 cells were tested. The effects of SI-4650 on apoptosis, migration and invasion were investigated. The effects of SI-4650 on Bax, Bcl-2, Caspase3, E-cadherin, N-cadherin, Vimentin, matrix metalloproteinase 2 ( MMP2) and MMP 9 expression levels in SKVO-3 cells were detected. Results: Comparison between blank control group and experimental groups,SI-4650 could improve the content of SI-4650 in SKVO-3 cells. SI-4650 could inhibit the activity of SMO (P＜0.01), reduce the ROS (P＜0.01)and polyamine content in SKVO-3 cells (P＜0.01). Treatment of SKVO-3 cells with SI-4650 inhibited the proliferation (the inhibition rate was 32.27% and 47.31% in experimental groups), caused S-phase cell cycle arrest (P＜0.01) and induced apoptosis (P＜0.01). The expressions of Bax and c-Caspase3 in SKVO-3 cells were increased (P＜0.01),the content of Bcl-2 was decreased (P＜0.01), and the mitochondrial membrane potential was decreased (P＜0.01), and the number of apoptotic cells was increased(31.41% and 43.51% in experimental groups). At the same time, SI-4650 could change the expression levels of EMT-related factors, increased the expression level of E-cad , decreased the expression levels of N-cad, Vimentin, MMP-2 and MMP-9, and inhibited the migration and invasion of SKVO-3 cells. Conclusion: SI-4650 can effectively inhibit proliferation, invasion and metastasis of human ovarian cancer SKVO-3 cells, and the mechanism may be related to its ability to depress the activity of SMO, interfere polyamine metabolism and induce cell cycle arrest, mitochondrial apoptosis and inhibit EMT. This study reveals potential application of SI-4650 in the treatment of ovarian cancer.

[Distribution Characteristics of Microplastics in Ice Sheets and Its Response to Salinity and Chlorophyll a in the Lake Wuliangsuhai].

There are sparse reports on the distribution of microplastics in the ice sheets of freshwater lakes. In this study, the abundance, color, shape, and species of microplastics in the ice sheet of Lake Wuliangsuhai were characterized using field sampling and microscope observations. Fourier-transform infrared spectroscopy (FTIR) and correlation analysis were used to examine the distribution of microplastics contained in the lake and its relationships with salinity and chlorophyll a. The results show that the average abundance of microplastics in the Lake Wuliangsuhai ice sheet is 56.75-141 n·L-1, which is approximately 10-100 times higher than in the surface water of the Lake Wuliangsuhai. Fibers were the most common type of microplastics followed by fragments. Overall abundance showed a decreasing trend in the downstream horizontal direction and was positively correlated with salinity in the vertical direction. The abundance of microplastic in the surface ice and bottom ice was greater than in the middle of the ice and near bottom of the ice. There was no correlation between the abundance of microplastic and the concentration of chlorophyll a. In addition, due to the capturing effect of the ice, microplastic particles are temporarily stored in the ice sheet in winter, which are released into water in spring. This study provides baseline information to inform microplastic pollution control measures in Lake Wuliangsuhai.

Nanopore Formation and Structural Changes in Black Shale During the Initial Weathering Stage: A Longmaxi Formation Profile in Northwestern Hunan, China.

Understanding the controls on composition changes and porosity evolution in the critical zone of shale remains a major challenge. The aim of the present study is to develop a model of the changes in mineral compositions, chemical compositions and nanopore formation in shale during the initial weathering stage. To understand these processes, we selected a Silurian shale profile rich in pyrite and organic matter located in South China. Based on X-ray diffraction (XRD) and bulk elemental data, the variations in mineralogical and chemical compositions with depth were studied. To characterize the full pore size spectrum and to gain insight into the nature of secondary pores and their relationship with weathering, nuclear magnetic resonance (NMR) measurements and petrographic observations were combined with scanning electron microscopy (SEM) imaging. The results show that Al and K are enriched slightly, while Ca and Na are depleted in the upper part of the weathering profile. Si, Mn and Ti are relatively stable from the bottom to the top of the profile. Quartz, feldspar, mica, illite and chlorite are the main minerals in the parent rock, and they are relatively stable along the profile. The rock density gradually decreases from 2.6 g/cm³ to 2.1 g/cm³ from the bottom to the top, and the color of the shales changes from black to grayish yellow, but no secondary minerals are detected. The chemical weathering of black shale is dominated by the oxidation of pyrite and organic matter, giving rise to color variation and nanopore formation. The increase in interparticle pores at the nanometer-micron scale is initiated by the dissolution of easily weathered components such as organic matter and pyrite. The removal of clay minerals and tiny particles by groundwater seepage may be the main cause of porosity enhancement during the initial weathering stage. This study suggests that nanoporosity may play an important role in the process of fluid-rock interaction within black shale during the initial weathering stage.

[Effects of a novel polyamine metabolic enzyme inhibitor SI-4650 on proliferation of colon cancer CT-26 cells and its mechanism].

OBJECTIVE: To investigate the effects of a novel polyamine metabolism enzyme inhibitor SI-4650 on autophagy and apoptosis of colon cancer CT-26 cells as well as their correlation. METHODS: CT-26 cells treated with 40, 80 µmol·L-1 SI-4650 alone or in combination with 3-MA were used as experimental group. CT-26 cells treated with 0 µmol·L-1 SI-4650 alone or in combination with 3-MA were used as control group. Chemiluminescence was used to analyze the effect of SI-4650 on spermine oxidase (SMO) and acetylpolyamine oxidase(APAO) activity. High performance liquid chromatography (HPLC) was performed to detect cellular polyamine content.The CCK8 method was used to detect the inhibitory effect of SI-4650 on proliferation of CT-26 cells. PI single-staining/flow cytometry (FCM) were used to analyze cell cycle. Western blot were used to analyze autophagy. Apoptosis was analyzed by PI/FITC-Annexin V double staining, JC-1 fluorescent probe and Fluo-3 AM calcium ion fluorescent probe combined with flow cytometry and Western blot. RESULTS: CCK8 assay showed that 24-,48-,72-hours treated with SI-4650 all could inhibit the proliferative activity of CT-26 cells in a dose- and time-dependent manner (P＜0.01) . The inhibition rate was 36.98% and 46.91% in 40 µmol·L-1 SI-4650 group and 80 µmol·L-1 SI-4650 group respectively. SI-4650 could significantly inhibit the activities of SMO and APAO interfere with polyamine metabolism and reduce the content of total polyamine in CT-26 cells (P＜0.01). SI-4650 could block CT-26 cells in G0/G1 phase, significantly reduce the number of cells in S phase(P＜0.01), and lead to a significant increase in the contents of autophagy-related Beclin-1, LC3-II in CT-26 cells(P＜0.01); At the same time, the concentration of calcium in CT-26 cells was increased, the mitochondrial membrane potential was decreased, the expressions of c-PARP and Bax were increased, the content of Bcl-2 was decreased, and the number of apoptotic cells was increased. After SI-4650 combined with autophagy inhibitor 3-MA treatment of CT-26 cells, the level of autophagy, the apoptosis-related protein, mitochondrial membrane potential and calcium ion concentration were decreased, and the number of apoptotic cells was decreased. CONCLUSION: SI-4650 has the pharmacological activity of killing colon cancer CT-26 cells, and its mechanism may be related to the interference of polyamine metabolism and induction of cell apoptosis and autophagy. In this process, autophagy is inhibited to block apoptosis, autophagy and apoptosis combined to kill tumor cells.

[Occurrence Characteristics and Quality Estimation of Microplastics in Drainage Ditches in Hetao Irrigation District of Inner Mongolia].

Microplastic pollution due to land runoff has gained increasing attention as it is closely associated with human beings. In this study, we analyzed the occurrence characteristics of microplastics in drainage channel and main drainage channel in Hetao irrigation district of Inner Mongolia and estimated its quality. Through field sampling, the density separation of suspension method and microscope observation, Fourier infrared spectrum measurement, and proportional flow method, the abundance distribution, shape, color, particle size, and chemical composition of microplastics in the water body and sediment of the drainage channel and main drainage channel in the Hetao irrigation district were identified. The mass of microplastics transported in the main drainage channel was also estimated. The results showed that the value range of microplastic abundance in the water body of the drainage channel and the main drainage channel in Hetao irrigation district was 2880-11200 n ·m-3, and the value range of microplastic abundance in the sediment was 100-292 n ·kg-1. Fiber was the most common microplastic form, occupying 34.98%-70.39% and 42.24%-58.56% in the water and sediment, respectively. The color of microplastics was mainly transparent, which occupied 46.43%-61.51% and 40.41%-57.44% in the water and sediment, respectively. The largest particle size of microplastics was<0.5 mm, accounting for 46.43%-61.51% and 43.27%-54.79% in the water and sediment microplastics, respectively. It was concluded that polyethylene was the most common type (43%), followed by polystyrene (34%) and polypropylene (16%) using Fourier infrared spectroscopy. It was estimated that the main drainage channel in the Hetao irrigation district could transport 116.06 kg of microplastics into Lake Ulansuhai every day, and a serious microplastic pollution effect was generated due to the accumulation of microplastics in Lake Wulangsuhai. This study can provide reference for the pollution of microplastics in Hetao irrigation district of Inner Mongolia.

Apoptotic Melanoma B16-F1 Cells Induced by Lidamycin Could Initiate the Antitumor Immune Response in BABL/c Mice.

In the process of tumor cell apoptosis induced by specific regents, calreticulin (CRT) was transferred from endoplasmic reticulum (ER) onto the cell membrane. These tumor cells, when used as the cellular vaccine to immunize experimental animals, could initiate effective antitumor immunoresponse against homologous tumor cells. This is referred to as immunogenic cell death. Lidamycin (LDM) is an enediyne antibiotic, which has extremely potent cytotoxicity to cancer cells. In this study, the mouse melanoma B16-F1 cancer cells were used to investigate the ability of LDM in promoting immunogenic cell death. Our data showed that LDM could induce apoptosis of B16-F1 cancer cells, accompanied by CRT translocation onto the cell membrane. These LDM-treated B16-F1 cells could be recognized and phagocytosed more efficiently by macrophage and dendritic cells. When the LDM-treated apoptotic B16-F1 cells were used as a whole-cell tumor vaccine to immune mice, the mice obtained resistance against rechallenged B16-F1 living cells. At the same time, the specific antitumor immune response was observed in these vaccinated mice. The splenocytes from the mice vaccinated with LDM-treated B16-F1 cells showed significantly enhanced NK lymphocyte activities and also faster growth rate and increased secretion of IFN-γ when encountering the cellular antigens from B16-F1 cells. All these results suggested that LDM could promote immunogenic cell death in B16-F1 cells, and these LDM-treated B16-F1 cells could be used as a sort of cell vaccine to initiate effective antitumor immunoresponse in mice.

Polyamine analog TBP inhibits proliferation of human K562 chronic myelogenous leukemia cells by induced apoptosis.

The aim of the present study was to investigate the effects of the novel polyamine analog tetrabutyl propanediamine (TBP) on the growth of K562 chronic myelogenous leukemia (CML) cells and the underlying mechanism of these effects. MTT was used for the analysis of cell proliferation and flow cytometry was performed to analyze cell cycle distribution. DNA fragmentation analysis and Annexin V/propidium iodide double staining were used to identify apoptotic cells. The activity of the key enzymes in polyamine catabolism was detected using chemiluminescence. TBP can induce apoptosis and significantly inhibit K562 cell proliferation in a time- and dose-dependent manner. TBP treatment significantly induced the enzyme activity of spermine oxidase and acetylpolyamine oxidase in K562 cells, and also enhanced the inhibitory effect of the antitumor drug doxorubicin on K562 cell proliferation. As a novel polyamine analog, TBP significantly inhibited proliferation and induced apoptosis in K562 cells by upregulating the activity of the key enzymes in the polyamine catabolic pathways. TBP also increased the sensitivity of the K562 cells to the antitumor drug doxorubicin. These data indicate an important potential value of TBP for clinical therapy of human CML.

[Preparation and identification of monoclonal antibody against human spermine oxidase].

AIM: To prepare mouse anti-human spermine oxidase (anti-hSMO) monoclonal antibody (mAb) and testify its application in the biological techniques including Western blotting and immunohistochemistry. METHODS: Plasmid pET-15b/SMO was first transferred into BL21 (DE3), and then SMO recombinant protein with 6×His tag was induced to express by IPTG and purified by Ni-NTA resin. The purified recombinant SMO was used to immunize BALB/c mouse. The spleen cells from the immunized mouse were harvested and hybridized with Sp2/0 myeloma cells to obtain a hybridoma cell line that could efficiently synthesize and secret anti-SMO mAb. The titer and antigen specificity of this antibody were identified by ELISA, Western blotting and immunohistochemistry. RESULTS: We successfully obtained the hybridoma cell line which could stably secret anti-SMO mAb. The mAb was of a high titer and antigen specificity and could be used in ELISA, Western blotting, and immunohistochemistry for SMO. CONCLUSION: The mouse anti-hSMO mAB with a high antigen specificity has been prepared successfully and used for a variety of bio-analytical techniques.

[Expression and functional analysis of CRT-E2-EGFP fusion protein in B16 cells].

AIM: To detect the expression of the Calreticulin and HPV E2 Fusion Protein in B16, and study the effects on proliferation and apoptosis of B16 cell lines in vivo. METHODS: To construct eukaryotic fluoresce expression vector pEGFP-CRT-E2, pEGFP-CRT and pEGFP-E2. Then the recombinant plasmids were transfected into B16 cells by Lipofectamine 2000. The expression of proteins was detected by Western blot. The location of different GFP fusion proteins in B16 was tested by inverted fluoresce microscope. Flow cytometry was applied to detect the effects of fusion proteins on the growing of B16 and then the apoptosis effects of B16 induced by different proteins were observed. RESULTS: The correctly constructed recombinant plasmid pEGFP-CRT-E2 and the expression of CRT-E2 gene could be detected in B16 cells. Apoptosis of B16 cells could be detected after the transient transfection. Meanwhile, the apoptosis rate of B16 cells transfected by pEGFP-CRT-E2 was much higher than that of control cells. And cell cycle G1/G0 arrest was also found (P<0.01). CONCLUSION: The eukaryotic expression plasmid pEGFP-CRT-E2 is successfully constructed and it could correctly express the fusion protein in B16 cells. And the B16 cells transfected by plasmid pEGFP-CRT-E2 could induce apoptosis.

Influence of HBcAg in liver cell plasma on expression of transforming growth factor-beta 1 in liver tissue of low-grade chronic hepatitis B patients.

AIM: To study the influence of HBcAg on the expression of transforming growth factor-beta 1 (TGF-beta1) in liver tissue of low-grade chronic hepatitis B (CHB) patients. METHODS: The expression of TGF-beta1 and HBcAg in liver samples from 93 low-grade CHB patients was detected by immunohistochemistry and valuated by semi-quantitative scoring. RESULTS: In the 93 low-grade CHB patients, HBcAg was expressed in cell plasma but not in the liver tissue. There was no significant difference between the two groups. CONCLUSION: The expression of TGF-beta1 is not related with HBcAg expressed as plasma type in the tissues of low-grade CHB patients.

[The relationship between acute rejection and expression of sCD30 for the patients after kidney transplantation].

OBJECTIVE: To study the relationship between the sCD30 and acute rejection. METHODS: We tested the sCD30 level in serum for 58 cases with kidney transplantation before and the 7th day and 28th day after operation by ELISA. 31 healthy individual for control group, and simultaneously recorded the incidence of rejection after kidney transplantation. RESULTS: The results showed that there is an obviously relation before kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 4.843, P = 0.028, P < 0.05). There is a significantly relation at the 7th day after kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 7.201, P = 0.007, P < 0.01). There is no obviously relation at 28th day after kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 2.095, P = 0.148, P > 0.05). CONCLUSION: The results suggested that the expressions of sCD30 are related to acute rejection. We speculated that the expressions of sCD30 could play an important role in acute rejection.