Alantolactone Induced Apoptosis and DNA Damage of Cervical Cancer through ATM/CHK2 Signaling Pathway.

Traditional Chinese Medicine, known for its minimal side effects and significant clinical efficacy, has attracted considerable interest for its potential in cancer therapy. In particular, Inula helenium L. has demonstrated effectiveness in inhibiting a variety of cancers. This study focuses on alantolactone (ALT), a prominent compound from Inula helenium L., recognized for its anti-cancer capabilities across multiple cancer types. The primary objective of this study is to examine the influence of ALT on the proliferation, apoptosis, cell cycle, and tumor growth of cervical cancer (CC) cells, along with its associated signaling pathways. To determine protein expression alterations, Western blot analysis was conducted. Furthermore, an in vivo model was created by subcutaneously injecting HeLa cells into nude mice to assess the impact of ALT on cervical cancer. Our research thoroughly investigates the anti-tumor potential of ALT in the context of CC. ALT was found to inhibit cell proliferation and induce apoptosis in SiHa and HeLa cell lines, particularly targeting ataxia-telangiectasia mutated (ATM) proteins associated with DNA damage. The suppression of DNA damage and apoptosis induction when ATM was inhibited underscores the crucial role of the ATM/cell cycle checkpoint kinase 2 (CHK2) axis in ALT's anti-tumor effects. In vivo studies with a xenograft mouse model further validated ALT's effectiveness in reducing CC tumor growth and promoting apoptosis. This study offers new insights into how ALT combats CC, highlighting its promise as an effective anti-cervical cancer agent and providing hope for improved treatment outcomes for CC patients.

Mass spectrometry-based proteomic landscape of rice reveals a post-transcriptional regulatory role of N6-methyladenosine.

Rice is one of the most important staple food and model species in plant biology, yet its quantitative proteomes are largely uncharacterized. Here we quantify the relative protein levels of over 15,000 genes across major rice tissues using a tandem mass tag strategy followed by intensive fractionation and mass spectrometry. We identify tissue-specific and tissue-enriched proteins that are linked to the functional specificity of individual tissues. Proteogenomic comparison of rice and Arabidopsis reveals conserved proteome expression, which differs from mammals in that there is a strong separation of species rather than tissues. Notably, profiling of N6-methyladenosine (m6A) across the rice major tissues shows that m6A at untranslated regions is negatively correlated with protein abundance and contributes to the discordance between RNA and protein levels. We also demonstrate that our data are valuable for identifying novel genes required for regulating m6A methylation. Taken together, this study provides a paradigm for further research into rice proteogenome.

Hypoxic preconditioning accelerates the healing of ischemic intestinal injury by activating HIF-1α/PPARα pathway-mediated fatty acid oxidation.

Hypoxic preconditioning (HPC) has been shown to improve organ tolerance to subsequent severe hypoxia or ischemia. However, its impact on intestinal ischemic injury has not been well studied. In this study, we evaluated the effects of HPC on intestinal ischemia in rats. Intestinal rehabilitation, levels of fatty acid oxidation (FAO) by-products, intestinal stem cells (ISCs), levels of hypoxia-inducible factor 1 subunit α (HIF-1α) and its downstream genes such as peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyltransferase 1a (CPT1A) were assessed at distinct time intervals following intestinal ischemia with or without the interference of HIF-1α. Our data showed that HPC facilitates the restoration of the intestinal structure and enhances the FAO, by boosting intestinal stem cells. Additionally, HIF-1α, PPARα, and CPT1A mRNA and their protein levels were generally up-regulated in the small intestine of HPC rats as compared to the control group. Our vitro experiment also shows low-oxygen induces highly levels of HIF-1α and its downstream genes, with a concurrent increase in FAO products in IEC-6 cells. Furthermore, the above phenomenon could be reversed by silencing HIF-1α. In conclusion, we hypothesize that HPC can stimulate the activation of intestinal stem cells via HIF-1α/PPARα pathway-mediated FAO, thereby accelerating the healing process post ischemic intestinal injury.

TSLP enhances progestin response in endometrial cancer via androgen receptor signal pathway.

BACKGROUND: The enriched proteins within in vitro fertilisation (IVF)-generated human embryonic microenvironment could reverse progestin resistance in endometrial cancer (EC). METHODS: The expression of thymic stromal lymphopoietin (TSLP) in EC was evaluated by immunoblot and IHC analysis. Transcriptome sequencing screened out the downstream pathway regulated by TSLP. The role of TSLP, androgen receptor (AR) and KANK1 in regulating the sensitivity of EC to progestin was verified through a series of in vitro and in vivo experiments. RESULTS: TSLP facilitates the formation of a BMP4/BMP7 heterodimer, resulting in activation of Smad5, augmenting AR signalling. AR in turn sensitises EC cells to progestin via KANK1. Downregulation of TSLP, loss of AR and KANK1 in EC patients are associated with tumour malignant progress. Moreover, exogenous TSLP could rescue the anti-tumour effect of progestin on mouse in vivo xenograft tumour. CONCLUSIONS: Our findings suggest that TSLP enhances the sensitivity of EC to progestin through the BMP4/Smad5/AR/KANK1 axis, and provide a link between embryo development and cancer progress, paving the way for the establishment of novel strategy overcoming progestin resistance using embryo original factors.

SIM2: Its Prognostic Significance and Oncogenic Role in Endometrial Carcinoma.

Background: Endometrial carcinoma ranks as the second most widespread malignancy affecting the reproductive system in females. Effective prognostic biomarkers are required to further improve survival rates for patients. Single-minded homolog 2 (SIM2) is known to participate in neurogenesis as a transcription factor. However, the potential role of SIM2 in endometrial carcinoma remains elusive. Methods: Multiple public databases, including TIMER2.0, GEIPA2, UALCAN, LinkedOmics, BioGRID, DAVID and cBioPortal, were used to investigate SIM2 mRNA expression, SIM2-associated genes, PPI network, functional enrichment analysis, SIM2 gene alterations and methylation. The association between SIM2 expression and immune cell infiltrates was explored using GSVA. The effects of gene alterations and methylation on patient survival and CD8+T infiltration were examined using GSCA. Moreover, the prognostic potential of SIM2 was evaluated using COX regression, ROC curves and a nomogram model. Finally, the differential expression and function of SIM2 in UCEC were explored using qPCR, WB, CCK8 and Transwell assays. Results: Our findings revealed the heightened expression of SIM2 in endometrial carcinoma, and that its DNA methylation and CNV alterations were correlated with immune infiltration and patients' prognosis. Additionally, functional enrichment revealed the involvement of SIM2 in transcription regulation and signal transduction. Moreover, we performed cell-based experiments to corroborate the oncogenic function of SIM2 in facilitating cell proliferation, migration and invasion. Conclusion: Collectively, these results suggest that SIM2 holds promise as both a potential prognostic indicator and a viable treatment target for endometrial carcinoma.

Bruceine A inhibited breast cancer proliferation and metastasis by inducing autophagy via targeting PI3K-AKT signaling pathway.

Although there have been significant advances in cancer treatment, the urgent need to inhibit breast cancer metastasis remained unmet. Bruceine A (BA) is a natural compound extracted from Bruceae Fructus and has long been recognized to have antitumor effects with high safety and biocompatibility. However, the mechanisms and/or targets of BA for metastatic breast cancer treatment are still not fully elucidated. In this study, we systematically investigated the effects of BA on inhibition of breast cancer metastasis and its underlying mechanisms. We found that, in addition to its cytotoxic effects, BA significantly inhibited the invasion and migration capabilities of two types of breast cancer cell lines (MDA-MB-231 and MCF-7) while concurrently promoting apoptosis in these cells. Further mechanistic studies revealed that, by targeting the canonical PI3K-AKT signaling pathway, BA initiated autophagy of both types of breast cancer cell lines in vitro. In vivo results further confirmed the in vitro findings, manifested by shrinkage of size and weight of breast tumor as well as initiation of autophagy (indicated by upregulation of LC3I/II) through targeting PI3K-AKT pathway on mice model. These data collectively demonstrated the potential of BA in antimetastasis of breast cancer cells, suggesting its future clinical transformation in metastatic breast cancer therapy.

NEDD4L facilitates granulosa cell ferroptosis by promoting GPX4 ubiquitination and degradation.

Background: Polycystic ovary syndrome (PCOS) is an androgen disorder and ovarian dysfunction disease in women of reproductive age. The cell death of granulosa cells (GCs) plays an important role in the development of PCOS. However, the mechanism of GC death is still unclear. Methods: In the current study, NEDD4L was found to be elevated in PCOS GEO (Gene Expression Omnibus) databases and mouse models. The cell viability was analyzed by CCK-8 and FDA staining. The expression of ferroptosis markers was assessed by ELISA and immunofluorescence. The direct interaction of GPX4 and NEDD4L was verified by co-immunoprecipitation assay. Result: Functionally, results from CCK-8 and FDA staining demonstrated that NEDD4L inhibited the cell viability of KGN cells and NEDD4L increased the levels of iron, malonyldialdehyde, and reactive oxygen species and decreased glutathione levels. Moreover, the cell death of KGN induced by NEDD4L was blocked by ferroptosis inhibitor, suggesting that NEDD4L regulates KGN cell ferroptosis. Mechanistically, NEDD4L directly interacts with GPX4 and promotes GPX4 ubiquitination and degradation. Conclusion: Taken together, our study indicated that NEDD4L facilitates GC ferroptosis by promoting GPX4 ubiquitination and degradation and contributes to the development of PCOS.

Development and validation of the planktonic index of biotic integrity (P-IBI) for Qin River, a main tributary of the Yellow River in China.

To evaluate the ecosystem health of Qin River, a main tributary of the Yellow River, a planktonic index of biotic integrity (P-IBI) that includes phytoplankton and zooplankton was established based on five metrics using a dataset covering 61 sampling sites in Qin River and its largest tributary the Dan River from October to November 2020. First, an index based on land use pattern and water quality was constructed to select reference sites and impaired sites. Then, five of an initial 38 candidate metrics (phytoplankton density, Palmer algal genus pollution index, zooplankton biomass/phytoplankton biomass, zooplankton Margalef richness index, and zooplankton Simpson diversity index) were selected to establish P-IBI based on their ranges, sensitivity, and redundancy. Finally, five statuses (excellent, good, fair, poor, and very poor) were classified by ratio score method on the basis of their final P-IBI scores. Sites with "excellent and good" and "poor and very poor" status accounted for 26.2% and 49.2%, respectively. "Very poor" sites were mainly located in the Dan River, and "poor" sites were mainly located in the middle reach of the Qin River and upper-middle reach of the Dan River in Jincheng region. Significantly negative correlations between Cl-, SO42-, and F- concentrations and P-IBI values indicated that the P-IBI might reflect domestic and industrial wastewater pollution in the Qin and Dan River in Jincheng region. The P-IBI strongly differentiated reference and impaired sites, suggesting the suitability of the index in the study.

Single-cell RNA-seq of Lotus japonicus provide insights into identification and function of root cell types of legume.

The roots of legume plant play a crucial role in nitrogen fixation. However, the transcriptomes of different cell types of legume root and their functions remain largely unknown. Here, we performed single-cell RNA sequencing and profiled more than 22,000 single cells from root tips of Lotus japonicus, a model species of legume. We identified seven clusters corresponding to seven major cell types, which were validated by in situ hybridization. Further analysis revealed regulatory programs including phytohormone and nodulation associated with specific cell types, and revealed conserved and diverged features for the cell types. Our results represent the first single-cell resolution transcriptome for legume root tips and a valuable resource for studying the developmental and physiological functions of various cell types in legumes.

Progestin Resistance and Corresponding Management of Abnormal Endometrial Hyperplasia and Endometrial Carcinoma.

With a younger tendency in morbidity age, endometrial cancer (EC) incidence has grown year after year. Worse, even more commonly occurring is endometrial hyperplasia (EH), which is a precancerous endometrial proliferation. For young women with early EC and EH who want to preserve fertility, progestin therapy has been utilized as a routine fertility-preserving treatment approach. Nevertheless, progestin medication failure in some patients is mostly due to progestin resistance and side effects. In order to further analyze the potential mechanisms of progestin resistance in EH and EC, to provide theoretical support for effective therapeutic strategies, and to lay the groundwork for searching novel treatment approaches, this article reviews the current therapeutic effects of progestin in EH and EC, as well as the mechanisms and molecular biomarkers of progestin resistance, and systematically expounds on the potential therapeutic methods to overcome progestin resistance.

Androgen Signaling in Uterine Diseases: New Insights and New Targets.

Common uterine diseases include endometriosis, uterine fibroids, endometrial polyps, endometrial hyperplasia, endometrial cancer, and endometrial dysfunction causing infertility. Patients with uterine diseases often suffer from abdominal pain, menorrhagia, infertility and other symptoms, which seriously impair their health and disturb their lives. Androgens play important roles in the normal physiological functions of the uterus and pathological progress of uterine diseases. Androgens in women are synthesized in the ovaries and adrenal glands. The action of androgens in the uterus is mainly mediated by its ligand androgen receptor (AR) that regulates transcription of the target genes. However, much less is known about the signaling pathways through which androgen functions in uterine diseases, and contradictory findings have been reported. This review summarizes and discusses the progress of research on androgens and the involvement of AR in uterine diseases. Future studies should focus on developing new therapeutic strategies that precisely target specific AR and their related signaling pathways in uterine diseases.

Ovarian stimulation in IVF couples with severe male factor infertility: GnRH antagonist versus long GnRH agonist.

Objective: To examine the efficacy of gonadotropin releasing hormone (GnRH) antagonist (GnRH-ant) protocol and the long GnRH agonist (GnRH-a) protocol during in vitro fertilization (IVF) therapy in patients with severe male infertile factors. Methods: A total of 983 women with severe male factor infertility undergoing IVF therapy from 2017 to 2020 at one center were retrospectively analyzed. Patients were divided into the GnRH-ant group (n=527) and the GnRH-a group (n=456) according to their ovarian stimulation protocols. Patient baseline characteristics, ovarian stimulation characteristics, and clinical pregnancy outcomes were compared between the groups. The live birth rate was considered the main pregnancy outcome. Results: GnRH-a group had a higher live birth rate compared with the GnRH-ant group (41.0% versus 31.3%, p=0.002). Moreover, the implantation (32.8% vs. 28.1%, p=0.033), biochemical pregnancy (52.4% versus 44.8%, p=0.017), clinical pregnancy (49.3% versus 39.7%, p=0.002) and ongoing pregnancy rates (43.2% vs. 34.9%, p=0.008) were higher in GnRH-a group. For patients with one embryo transferred, the GnRH-a group demonstrated higher live birth (37.0% vs. 19.4%, p=0.010) and ongoing pregnancy rate (38.9% vs. 24.5%, p=0.046) than the GnRH-ant group. Among patients with two embryos transferred, the live birth rate was also higher in the GnRH-a group than in the GnRH-ant group, with no statistical difference. No significant differences were observed in the biochemical abortion rate, clinical miscarriage rate, early miscarriage rate, late miscarriage rate, heterotopic pregnancy rate, twin pregnancy rate, and birth sex ratio between the two groups. Conclusion: For individuals with severe male infertility undergoing IVF, the GnRH-a protocol is considered a more efficient and feasible strategy with a higher live birth rate compared to the GnRH-ant protocol, especially in single embryo transfer.

[Characteristics of Phytoplankton Community Structure and Their Relationships with Environmental Factors in Autumn in Qinhe River Basin of Jincheng Region].

In October-November 2020, the phytoplankton and the aquatic environment from 62 sites in the mainstream of the Qinhe River and the largest tributary of the Qinhe River (Danhe River) in the Jincheng region were investigated to clarify the spatial pattern of phytoplankton communities and their driving factors. A total of 7 phyla and 47 species of phytoplankton were identified in the Qinhe River basin and were composed of Cryptophyta, Chlorophyta, Pyrrophyta, Chrysophyta, Bacillariophyta, Cyanophyta, and Crytophyta. Six dominant species in the Qinhe River included:Chlorella vulgaris, Cryptomonas erosa, Chroomonas acuta, Cyclotella stelligera, Chlorococcum, and Euglena viridis. Six dominant species in the Danhe River included:C. erosa, Frustulia vulgaris, E. viridis, C. vulgaris, Trachelomonas oblonga Lemm, and C. stelligera. The Shannon-Wiener diversity index (H') varied from 0.35 to 3.15, with a mean value 1.40. The Pielou evenness index (J) varied from 0.24 to 1.00, with a mean value of 0.68. H' values in the Qinhe River were higher than those in the Danhe River. J values were relatively low in the middle reaches of the Qinhe River and middle-low reaches of the Danhe River. The results in the Qinhe River through a canonical correspondence analysis (CCA) showed that the percent of forest land at a 300 m buffer was the driving factor of Chlorococcum in Chlorophyta, and nitrate, total phosphorus, and the percent of forest land at the 300 m buffer were the driving factors of E. viridis. Cyclotella stelligera was mainly influenced by the percent of urban land and water temperature, whereas C. vulgaris, C. erosa, and C. acuta were mainly influenced by the percent of farmland and residential land at the 300 m buffer. The results in the Danhe River via CCA showed that C. erosa and C. stelligera were mainly influenced by pH and sulfate, E. viridis was mainly influenced by the percent of urban land and grass land, T. oblonga Lemm was mainly influenced by chloride and the percent of forest land, F. vulgaris was mainly influenced by water temperature and the percent of farmland, and C. vulgaris was mainly influenced by ammonia and the percent of farmland.

Value of TCT combined with serum CA153 and CA50 in early diagnosis of cervical cancer and precancerous lesions.

Objectives: To determine the application value of thinprep cytologic test (TCT) combined with serum carbohydrate antigen 153 (CA153) and carbohydrate antigen 50 (CA50) detection in the early diagnosis and screening of cervical cancer and precancerous lesions. Methods: A total of 187 females with cervical lesions admitted to Shanghai 7th People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2017 to December 2018 were selected and divided into two groups: the cervical cancer group and the cervical precancerous lesion group, with 16 cases in the cervical cancer group and 171 cases in the cervical precancerous lesion group (cervical precancerous lesions were divided into 63 cases of the CNI group, 59 cases of the CNII group and 49 cases of the CNIII group). During the same period, 106 healthy females were selected as the healthy group. The serum tumor markers CA153 and CA50 of all subjects were detected by chemiluminescence method; The diagnostic value of TCT combined with serum CA153 and CA50 in cervical cancer and precancerous lesions was analyzed with colposcopy pathological diagnosis results as gold standard; ROC curve was drawn to evaluate the diagnostic value of serum TCT, CA153 and CA50 in cervical cancer and precancerous lesions. Results: The levels of serum CA153 and CA50 in the cervical cancer group were significantly higher than those in the cervical precancerous lesion group and the healthy group (p< 0.05), and the levels of serum CA153 and CA50 in the cervical precancerous lesion group were significantly higher than those in the healthy group (p< 0.05). The sensitivity of TCT, serum CA153 and serum CA50 in the single detection of cervical cancer and precancerous lesions was 95.93%, 97.54% and 96.00%, the specificity was 59.41%, 60.23%, 60.12%, the accuracy was 74.74%, 75.77%, 75.43%, the positive predictive value was 62.03%, 63.64%, 63.10%, and the negative predictive value was 96.22%, 97.17% and 95.28%, respectively. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of TCT combined with serum CA153 and CA50 were 96.77%, 73.19%, 85.67%, 80.21% and 95.28%, respectively. ROC curve showed that the area under the curve (AUC) of TCT and serum CA153 and CA50 in the single detection of cervical cancer and precancerous lesions was 0.791, 0.864 and 0.787, respectively, the AUC of combined detection of TCT and serum CA153 and CA50 in patients with cervical cancer and precancerous lesions was 0.877, which was significantly higher than that of single detection (p< 0.05). Conclusions: TCT combined with serum CA153 and CA50 has been reported as a treatment regimen with high accuracy, which has a high diagnostic efficiency for early diagnosis of cervical cancer and precancerous lesions, and can significantly improve the sensitivity.

Substrate-dependent modulation of the leukotriene A4 hydrolase aminopeptidase activity and effect in a murine model of acute lung inflammation.

The aminopeptidase activity (AP) of the leukotriene A4 hydrolase (LTA4H) enzyme has emerged as a therapeutic target to modulate host immunity. Initial reports focused on the benefits of augmenting the LTA4H AP activity and clearing its putative pro-inflammatory substrate Pro-Gly-Pro (PGP). However, recent reports have introduced substantial complexity disconnecting the LTA4H modulator 4-methoxydiphenylmethane (4MDM) from PGP as follows: (1) 4MDM inhibits PGP hydrolysis and subsequently inhibition of LTA4H AP activity, and (2) 4MDM activates the same enzyme target in the presence of alternative substrates. Differential modulation of LTA4H by 4MDM was probed in a murine model of acute lung inflammation, which showed that 4MDM modulates the host neutrophilic response independent of clearing PGP. X-ray crystallography showed that 4MDM and PGP bind at the zinc binding pocket and no allosteric binding was observed. We then determined that 4MDM modulation is not dependent on the allosteric binding of the ligand, but on the N-terminal side chain of the peptide. In conclusion, our study revealed that a peptidase therapeutic target can interact with its substrate and ligand in complex biochemical mechanisms. This raises an important consideration when ligands are designed to explain some of the unpredictable outcomes observed in therapeutic discovery targeting LTA4H.

Evaluation of the necessity of laparoscopic repair of a uterine scar defect for cesarean scar pregnancy.

OBJECTIVE: This study aimed to determine the risk factors associated with the necessity of laparoscopic scar defect repair for cesarean scar pregnancy (CSP). METHODS: We retrospectively analyzed 237 patients with CSP who were treated by ultrasound-guided suction curettage and/or laparoscopy in our hospital from April 2012 to November 2019. A total of 199 of these patients underwent ultrasound-guided suction curettage without uterine scar defect repair, while 38 of these patients underwent laparoscopic resection and uterine scar defect repair. We analyzed various clinical variables and compared the efficacy of treatment between the two groups. RESULTS: Gestational age, the maximum transverse diameter (MTD) of the gestational sac, myometrial thickness, the operation time, intraoperative blood loss, and the duration of the hospital stay were significantly different between the two groups. Gestational age, the MTD of the gestational sac, and myometrial thickness were independent risk factors for laparoscopic repair. CONCLUSIONS: Gestational age, the MTD of the gestational sac, and myometrial thickness are important factors associated with the necessity for laparoscopic repair of a uterine scar defect.

Construction of a ceRNA network of hub genes affecting immune infiltration in ovarian cancer identified by WGCNA.

BACKGROUND: Ovarian cancer is the leading cause of death among gynecological malignancies. Immunotherapy has demonstrated potential effects in ovarian cancer. However, few studies on immune-related prognostic signatures in ovarian cancer have been reported. This study aimed to identify hub genes associated with immune infiltrates to provide insight into the immune regulatory mechanisms in ovarian cancer. METHODS: Raw data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and University of California, Santa Cruz (UCSC) Xena websites. Single-sample gene set enrichment analysis (ssGSEA) and weighted gene co-expression network analysis (WGCNA) were used to identify hub genes. Kaplan-Meier analysis and differential expression analysis were applied to explore the real hub genes. RESULTS: Through ssGSEA and WGCNA, 7 hub genes (LY9, CD5, CXCL9, IL2RG, SLAMF1, SLAMF6, and SLAMF7) were identified. Finally, LY9 and SLAMF1 were recognized as the real hub genes in immune infiltrates of ovarian cancer. LY9 and SLAMF1 are classified as SLAM family receptors involved in the activation of hematopoietic cells and the pathogenesis of multiple malignancies. Furthermore, 12 lncRNAs and 43 miRNAs significantly related to the 2 hub genes were applied to construct a lncRNA-miRNA-mRNA ceRNA network. The lncRNA-miRNA-mRNA ceRNA network shows upstream regulatory sites of the 2 hub genes. CONCLUSIONS: These findings improve our understanding of the regulatory mechanism of and reveal potential immune checkpoints for immunotherapy for ovarian cancer.

Progranulin promotes osteogenic differentiation of periodontal membrane stem cells in both inflammatory and non-inflammatory conditions.

OBJECTIVE: The growth factor progranulin (PGRN) is widely expressed and plays important roles in anti-inflammatory signaling and bone regeneration. However, the anti-inflammatory and pro-osteogenic roles of PGRN in periodontitis are seldom studied. We used an in vitro model to investigate whether PGRN can promote osteogenic differentiation of periodontal ligament stem cells (PDLSCs). METHODS: PDLSCs were treated with PGRN (0 to 100 ng/mL) and the optimal concentrations required to induce proliferation and osteogenesis were identified. PDLSCs were cultured with 10 ng/mL tumor necrosis factor (TNF)-α, 25 ng/mL PGRN, or 10 ng/mL TNF-α + 25 ng/ml PGRN; untreated PDLSCs were used as controls. The effects of PGRN on PDLSC proliferation and osteogenic differentiation were assessed. RESULTS: PGRN (5, 25, and 50 ng/mL) promoted PDLSC proliferation and osteogenic differentiation, with the 25-ng/mL dose showing the largest effect. Furthermore, 25 ng/mL PGRN reversed inhibition of osteogenic differentiation by TNF-α. CONCLUSION: PGRN promotes PDLSC proliferation, osteogenic differentiation, and mineralization in both inflammatory and non-inflammatory conditions. The 25-ng/mL PRGN dose was the most suitable for inducing proliferation and osteogenesis. Further studies using animal models will be required to obtain pre-clinical evidence to support using PGRN as a treatment for periodontitis.

Nitrate sources and transformations along a mountain-to-plain gradient in the Taizi River basin in Northeast China.

Fifty-seven riverine samples in three typical regions, namely, upper mountainous (zone 1), middle hilly (zone 2), and lower plain (zone 3) regions, were collected in May (low flow) and August (high flow) of 2016, and chemical parameters and isotopes were analyzed to enrich the knowledge of riverine nitrate sources and transformations in the Taizi River basin. Results showed that NO3- concentrations in zone 3 were the highest, followed by zones 2 and 1. NO3-/Cl- molar ratios and nitrate dual isotopes indicated that NO3- was mainly from chemical fertilizer (CF) in zones 1 (57.0%) and 2 (43.1%) according to a Bayesian mixing model (SIAR) and mixed sources of CF, nitrification of soil organic nitrogen (SON), and manure and sewage (M&S) in zone 3 (92.8%), during the high-flow season. NO3- was mainly from CF and SON in zones 1 (76.7%) and 2 (74.0%), during the low-flow season. NO3-sources were different in the three rivers of zone 3 mainly due to various urban inputs. Contributions of CF, SON, and M&S increased by 13%, 8.3%, and 7.5% in zones 1, 2, and 3, respectively, from the low-flow to the high-flow season. NO3- in the Taizi River was mainly influenced by nitrification in soils, while no significant denitrification was found in the three zones. Measures for reducing NO3- inputs to rivers should be considered by improving effectively utilizing rate of chemical fertilizer and inhibit nitrification.

Impact of coronavirus disease 2019 on the mental health of university students in Sichuan Province, China: An online cross-sectional study.

Coronavirus disease 2019 is an emerging public health problem threatening not only the life but also the normal psychology of people. University students' mental health is the focus in the field of higher education. The coronavirus disease 2019 pandemic has brought into attention the mental health problems of this vulnerable group. The aim of this study was to assess the impact of coronavirus disease 2019 on the mental health of university students in Sichuan Province, China. We conducted a cross-sectional study from April 2020 to May 2020. The participants responded to an online questionnaire that included informed consent, basic information, 20-item Self Reporting Questionnaire (SRQ-20), and Self-Rating Anxiety Scale (SAS). We received 521 effective responses. The results included the following: 19.0% of respondents reported distress, and 31.5%, 8.1%, and 5.8% of them reported mild, moderate, and severe anxiety, respectively; respondents aged ≤ 22 years, medical students, and those who were in general health reported more distress than others; and medical students and those who paid more attention to pandemic information reported more anxiety than others. Findings suggest that the mental health of university students should be monitored during pandemic, especially for younger students, medical students, students in general health status, and those who paid too much attention to the news of the pandemic. Due to the limited sample representativeness, we must be cautious when generalizing these findings to other regions of China or other countries.