ALYREF-JunD-SLC7A5 axis promotes pancreatic ductal adenocarcinoma progression through epitranscriptome-metabolism reprogramming and immune evasion.

Pancreatic ductal adenocarcinoma (PDAC) is a kind of tumor lacking nutrients due to its poor vascularity and desmoplasia. Recent studies have shown that cancer cells might achieve growth advantage through epitranscriptome reprogramming. However, the role of m5C in PDAC was not fully understood. We found that Aly/REF export factor (ALYREF), a reader of m5C modification, was overexpressed in PDAC, and associated with bad prognosis. In addition, the ALYREF expression was negatively related to CD8+ T cells infiltration in clinical samples. ALYREF knockdown decreased tumor growth in vivo partly dependent of immunity. ALYREF silencing decreased SLC7A5 expression and subsequently inactivated mTORC1 pathway, resulting in decreased tumor proliferation. Mechanically, ALYREF specifically recognized m5C sites in JunD mRNA, maintained the stabilization of JunD mRNA and subsequently upregulated transcription of SLC7A5. Since SLC7A5 was a key transporter of large neutral amino acids (LNAAs), overexpression of SLC7A5 on tumor cells depleted amino acid in microenvironment and restricted CD8+ T cells function. Moreover, ALYREF-JunD-SLC7A5 axis was overexpressed and negatively related with survival through TMA assays. In conclusion, this research revealed the relationship between m5C modification, amino acid transportation and immune microenvironment. ALYREF might be a novel target for PDAC metabolic vulnerability and immune surveillance.

Image characteristics and main types of abnormal branching of fetal pulmonary artery in prenatal echocardiography - a retrospective study.

OBJECTIVES: To explore the image characteristics and main types of abnormal branching of fetal pulmonary artery in prenatal echocardiography. MATERIAL AND METHODS: A retrospective analysis of 41 cases diagnosed with abnormal branching of fetal pulmonary artery by prenatal echocardiography was made. The image characteristics of the abnormalities, their combination with intra- or extra-cardiac malformations and chromosomal anomalies were analyzed. RESULTS: The results of prenatal echocardiography showed that, among the 41 cases, 1) 4 cases were with anomalous origin of single pulmonary artery, 8 cases with pulmonary artery agenesis, 9 cases with pulmonary artery sling; 20 cases with crossed pulmonary arteries. 2) 11 cases were complicated with intracardiac malformations and 10 with extracardiac malformations. 3) Only 7 case underwent chromosomal examination and 1 tested abnormal. 4) Pregnancy outcomes: 25 fetuses were born and their abnormalities confirmed by echocardiography (MRI or surgery) to be consistent with prenatal ultrasound diagnosis; 16 cases had their pregnancy terminated due to their combination with other severe malformations, which were confirmed by pathological anatomy after induced abortion. CONCLUSIONS: Prenatal echocardiography can provide detailed images for the diagnosis of abnormal branching of fetal pulmonary artery, which can be complicated by intra- and extracardiac malformations and chromosomal anomalies and should be alerted.

Targeting cancer-associated fibroblast autophagy renders pancreatic cancer eradicable with immunochemotherapy by inhibiting adaptive immune resistance.

Accumulating evidence suggests that cancer-associated fibroblast (CAF) macroautophagy/autophagy is crucial in tumor development and may be a therapeutic target for pancreatic ductal adenocarcinoma (PDAC). However, the role of CAF autophagy during immune surveillance and cancer immunotherapy is unclear. The present study revealed that the inhibition of CAF autophagy suppresses in vivo tumor development in immune-deficient xenografts. This deletion compromises anti-tumor immunity and anti-tumor efficacy both in vitro and in vivo by upregulating CD274/PDL1 levels in an immune-competent mouse model. A block in CAF autophagy reduced the production of IL6 (interleukin 6), disrupting high desmoplastic TME and decreasing USP14 expression at the transcription level in pancreatic cancer cells. We further identify USP14 as the post-translational factor responsible for downregulating CD274 expression by removing K63 linked-ubiquitination at the K280 residue. Finally, chloroquine diphosphate-loaded mesenchymal stem cell (MSC)-liposomes, by accurately targeting CAFs, inhibited CAF autophagy, improving the efficacy of immunochemotherapy to combat pancreatic cancer.Abbreviation: AIR: adaptive immune resistance; ATRA: all-trans-retinoicacid; CAF: cancer-associated fibroblast; CD274/PDL1: CD274 molecule; CM: conditioned medium; CQ: chloroquine diphosphate; CyTOF: Mass cytometry; FGF2/bFGF: fibroblast growth factor 2; ICB: immune checkpoint blockade; IF: immunofluorescence; IHC: immunohistochemistry; IP: immunoprecipitation; MS: mass spectrometer; MSC: mesenchymal stem cell; PDAC: pancreatic ductal adenocarcinoma; TEM: transmission electron microscopy; TILs: tumor infiltrating lymphocytes; TME: tumor microenvironment; USP14: ubiquitin specific peptidase 14.

Effects of Polyethylene Glycol/Porous Silica Form-Stabilized Phase Change Materials on the Performance of Asphalt Binders.

The road performance and temperature-regulating properties of asphalt binders modified with novel polyethylene glycol (PEG)/porous silica (PS) form-stabilized phase-change materials (PEG/PS-fs-PCMs) were studied. PS and PEG were used as the supporting substance and PCMs. The results showed that PEG/PS-fs-PCMs could maintain a maximum weight percentage of 70% without leakage, at temperatures as high as 90 °C. The PEG/PS-fs-PCMs exhibited stable chemical structures, excellent thermal stability, high heat storage density, and suitable phase-change temperature. Based on conventional physical tests, the addition of PEG/PS-fs-PCMs can increase the viscosity and the degree of hardness of asphalt binders; thus, achieving an excellent comprehensive performance of the modified asphalt binder depends on determining the optimal dosage of PEG/PS-fs-PCMs. Additionally, incorporating PEG/PS-fs-PCM particles into the asphalt binder can enhance its ability to withstand permanent deformation at elevated temperatures, while PEG/PS-fs-PCMs mainly act as a filler, weakening the cohesive force of the asphalt molecules, and preventing the ductility of asphalt from expansion, according to DSR and BBR tests. Moreover, the use of PEG/PS-fs-PCMs can enhance the heat transfer properties of the asphalt binders, resulting in an improved temperature regulation performance. However, the accumulation of PEG/PS-fs-PCM particles on asphalt binders can negatively impact the storage stability of the modified asphalt binders, because of the difference in density between the two materials.

Association between creatine phosphokinase level within normal range and bone mineral density in adolescents.

Currently, it is unclear whether creatine phosphokinase (CPK) affects bone mineral density (BMD) in adolescents. We sought to clarify the relationship between CPK and total BMD in adolescents aged 12 to 19 years within normal values by conducting this study. A cross-sectional study was conducted using the 2011 to 2018 National Health and Nutrition Survey data to examine 1188 males (average age, 15.2 years) and 1629 females (average age, 15.4 years). In this study, CPK was the independent variable and total BMD was the outcome variable. In addition to using multivariate linear regression models, subgroup analyses were also conducted in order to examine the relationship between CPK levels and total BMD within normal ranges. Significant positive association was observed between the CPK levels and total BMD in adolescents (model 1: 0.0003 [0.0002, 0.0004], model 2: 0.0004 [0.0003, 0.0005] and model 3: 0.0004 [0.0003, 0.0004]). After adjusting for age, gender, race/ethnicity, body mass index, dietary protein intake, dietary protein intake, dietary fiber intake, poverty to income ratio, physical activities, total cholesterol, total protein, blood urea nitrogen, phosphorus, and serum calcium, CPK levels remained significantly associated with BMD (regression coefficients for quartiles 2 to 4 vs quartile1 were 0.0002, 0.0072, and 0.0154, respectively; P for trend <.001). The association was positive even when stratified by age, gender, and race. Further, adolescents aged 16 to 19 years were more likely to report positive relationships than adolescents aged 12 to 15 years. And the phase relationship between total BMD and CPK was further enhanced in boys. The results of our study show that CPK levels within the normal range are positively associated with total BMD in adolescents aged 12 to 19 years. Additionally, CPK may be a potential biomarker of bone health among adolescents.

Targeting leucine-rich repeat serine/threonine-protein kinase 2 sensitizes pancreatic ductal adenocarcinoma to anti-PD-L1 immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to immune checkpoint blockade therapy, and negative feedback of tumor immune evasion might be partly responsible. We isolated CD8+ T cells and cultured them in vitro. Proteomics analysis was performed to compare changes in Panc02 cell lines cultured with conditioned medium, and leucine-rich repeat kinase 2 (LRRK2) was identified as a differential gene. LRRK2 expression was related to CD8+ T cell spatial distribution in PDAC clinical samples and upregulated by CD8+ T cells via interferon gamma (IFN-γ) simulation in vitro. Knockdown or pharmacological inhibition of LRRK2 activated an anti-pancreatic cancer immune response in mice, which meant that LRRK2 acted as an immunosuppressive gene. Mechanistically, LRRK2 phosphorylated PD-L1 at T210 to inhibit its ubiquitination-mediated proteasomal degradation. LRRK2 inhibition attenuated PD-1/PD-L1 blockade-mediated, T cell-induced upregulation of LRRK2/PD-L1, thus sensitizing the mice to anti-PD-L1 therapy. In addition, adenosylcobalamin, the activated form of vitamin B12, which was found to be a broad-spectrum inhibitor of LRRK2, could inhibit LRRK2 in vivo and sensitize PDAC to immunotherapy as well, which potentially endows LRRK2 inhibition with clinical translational value. Therefore, PD-L1 blockade combined with LRRK2 inhibition could be a novel therapy strategy for PDAC.

Serum lipidomics-based study of electroacupuncture for skin wound repair in rats.

Lipid metabolism plays an important role in the repair of skin wounds. Studies have shown that acupuncture is very effective in skin wound repair. However, there is little knowledge about the mechanism of electroacupuncture. Thirty-six SD rats were divided into three groups: sham-operated group, model group and electroacupuncture group, with six rats in each group. After the intervention, orbital venous blood was collected for lipid metabolomics analysis, wound perfusion was detected and finally the effect of electroacupuncture on skin wound repair was comprehensively evaluated by combining wound healing rate and histology. Lipid metabolomics analysis revealed 11 differential metabolites in the model versus sham-operated group. There were 115 differential metabolites in the model versus electro-acupuncture group. 117 differential metabolites in the electro-acupuncture versus sham-operated group. There were two differential metabolites common to all three groups. Mainly cholesteryl esters and sphingolipids were elevated after electroacupuncture and triglycerides were largely decreased after electroacupuncture. The electroacupuncture group recovered faster than the model group in terms of blood perfusion and wound healing (p < 0.05). Electroacupuncture may promote rat skin wound repair by improving lipid metabolism and improving local perfusion.

Targeting MFAP5 in cancer-associated fibroblasts sensitizes pancreatic cancer to PD-L1-based immunochemotherapy via remodeling the matrix.

Highly desmoplastic and immunosuppressive tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) contributes to tumor progression and resistance to current therapies. Clues targeting the notorious stromal environment have offered hope for improving therapeutic response whereas the underlying mechanism remains unclear. Here, we find that prognostic microfibril associated protein 5 (MFAP5) is involved in activation of cancer-associated fibroblasts (CAFs). Inhibition of MFAP5highCAFs shows synergistic effect with gemcitabine-based chemotherapy and PD-L1-based immunotherapy. Mechanistically, MFAP5 deficiency in CAFs downregulates HAS2 and CXCL10 via MFAP5/RCN2/ERK/STAT1 axis, leading to angiogenesis, hyaluronic acid (HA) and collagens deposition reduction, cytotoxic T cells infiltration, and tumor cells apoptosis. Additionally, in vivo blockade of CXCL10 with AMG487 could partially reverse the pro-tumor effect from MFAP5 overexpression in CAFs and synergize with anti-PD-L1 antibody to enhance the immunotherapeutic effect. Therefore, targeting MFAP5highCAFs might be a potential adjuvant therapy to enhance the immunochemotherapy effect in PDAC via remodeling the desmoplastic and immunosuppressive microenvironment.

Immune Checkpoint Neuropilins as Novel Biomarkers and Therapeutic Targets for Pancreatic Cancer.

The traditional immune checkpoint blockade therapy benefits some patients with cancer, but elicits no response in certain cancers, such as pancreatic adenocarcinoma (PAAD); thus, novel checkpoints and effective targets are required. Here, we found that there was a higher Neuropilin (NRP) expression in tumor tissues as novel immune checkpoints, which was associated with poor prognosis and pessimistic responses to immune checkpoint blockade therapy. In the tumor microenvironment of PAAD samples, NRPs were widely expressed in tumor, immune and stromal cells. The relationship of NRPs with tumor immunological features in PAAD and pan-cancer was evaluated using bioinformatics methods; it was positively correlated with the infiltration of myeloid immune cells and the expression of most immune checkpoint genes. Bioinformatics analysis, in vitro and in vivo experiments suggested that NRPs exhibit potential immune-related and immune-independent pro-tumor effects. NRPs, especially NRP1, are attractive biomarkers and therapeutic targets for cancers, particularly PAAD.

KRAS mutations upregulate Runx1 to promote occurrence of head and neck squamous cell carcinoma.

Gene mutations play an important role in head and neck squamous cell carcinoma (HNSCC) by not only promoting the occurrence and progression of HNSCC but also affecting sensitivity to treatment and prognosis. KRAS is one of the most frequently mutated oncogenes, which has been reported to have a mutation rate from 1.7% to 12.7% and may lead to poor prognosis in HNSCC, but its role remains unclear. Here, we found that the KRAS mutation can promote HNSCC generation through synergism with 4-Nitroquinoline-1-Oxide(4NQO). Mechanistically, KRAS mutations can significantly upregulate Runx1 to promote oral epithelial cell proliferation and migration and inhibit apoptosis. Runx1 inhibitor Ro 5-3335 can effectively inhibit KRAS-mutated HNSCC progression both in vitro and in vivo. These findings suggest that the KRAS mutation plays an important role in HNSCC and that Runx1 may be a novel therapeutic target for KRAS-mutated HNSCC.

Identifying Genes Associated with Female Flower Development of Phellodendron amurense Rupr. Using a Transcriptomics Approach.

Phellodendron amurense Rupr., a species of Rutaceae, is a nationally protected and valuable medicinal plant. It is generally considered to be dioecious. With the discovery of monoecious P. amurense, the phenomenon that its sex development is regulated by epigenetics has been revealed, but the way epigenetics affects the sex differentiation of P. amurense is still unclear. In this study, we investigated the effect of DNA methylation on the sexual development of P. amurense. The young inflorescences of male plants were treated with the demethylation agent 5-azaC, and the induced female flowers were obtained. The induced female flowers' morphological functions and transcriptome levels were close to those of normally developed plants. Genes associated with the development of female flowers were studied by comparing the differences in transcriptome levels between the male and female flowers. Referring to sex-related genes reported in other plants, 188 candidate genes related to the development of female flowers were obtained, including sex-regulating genes, genes related to the formation and development of sexual organs, genes related to biochemical pathways, and hormone-related genes. RPP0W, PAL3, MCM2, MCM6, SUP, PIN1, AINTEGUMENTA, AINTEGUMENTA-LIKE6, AGL11, SEUSS, SHI-RELATED SEQUENCE 5, and ESR2 were preliminarily considered the key genes for female flower development. This study has demonstrated that epigenetics was involved in the sex regulation of P. amurense, with DNA methylation as one of its regulatory modes. Moreover, some candidate genes related to the sexual differentiation of P. amurense were obtained with analysis. These results are of great significance for further exploring the mechanism of sex differentiation of P. amurense and studying of sex differentiation of plants.

Exosomal miR-146b-5p derived from cancer-associated fibroblasts promotes progression of oral squamous cell carcinoma by downregulating HIPK3.

OBJECTIVES: Cancer-associated fibroblasts (CAFs) are vital constituents of the tumor microenvironment (TME) and play a predominant role in oral squamous cell carcinoma (OSCC) progression. We aimed to investigate the effect and mechanism of exosomal miR-146b-5p derived from CAFs on the malignant biological behavior of OSCC. MATERIALS AND METHODS: Illumina small RNA (sRNA) sequencing was conducted to determine the differential expression patterns of microRNAs (miRNAs) in exosomes derived from CAFs and normal fibroblasts (NFs). Transwell and cell counting kit-8 (CCK-8) assays and xenograft tumor models in nude mice were used to investigate the effect of CAF exosomes and miR-146b-p on the malignant biological behavior of OSCC. Reverse transcription quantitative real-time PCR (qRT-PCR), luciferase reporter, western blotting (WB) and immunohistochemistry assays were employed to investigate the underlying mechanisms involved in CAF exosomes that promote OSCC progression. RESULTS: We demonstrated that CAF-derived exosomes were taken up by OSCC cells and enhanced the proliferation, migration, and invasion ability of OSCC. Compared with NFs, the expression of miR-146b-5p was increased in exosomes and their parent CAFs. Further studies showed that the decreased expression of miR-146b-5p inhibited the proliferation, migration and invasion ability of OSCC cells in vitro and the growth of OSCC cells in vivo. Mechanistically, miR-146b-5p overexpression led to the suppression of HIKP3 by directly targeting the 3'-UTR of HIPK3, as confirmed by luciferase assay. Reciprocally, HIPK3 knockdown partially reversed the inhibitory effect of the miR-146b-5p inhibitor on the proliferation, migration, and invasion ability of OSCC cells and restored their malignant phenotype. CONCLUSIONS: Our results revealed that CAF-derived exosomes contained higher levels of miR-146b-5p than NFs, and miR-146b-5p overexpression in exosomes promoted the malignant phenotype of OSCC by targeting HIPK3. Therefore, inhibiting exosomal miR-146b-5p secretion may be a promising therapeutic modality for OSCC.

Targeting ubiquitin-specific protease 8 sensitizes anti-programmed death-ligand 1 immunotherapy of pancreatic cancer.

Programmed death-1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) help tumor cells evade immune surveillance, and are regarded as important targets of anti-tumor immunotherapy. Post-translational modification of PD-L1 has potential value in immunosuppression. Here, we identified that ubiquitin-specific protease 8 (USP8) deubiquitinates PD-L1. Pancreatic cancer tissues exhibited significantly increased USP8 levels compared with those in normal tissues. Clinically, the expression of USP8 showed a significant association with the tumor-node-metastasis stage in multiple patient-derived cohorts of pancreatic cancer. Meanwhile, USP8 deficiency could reduce tumor invasion and migration and tumor size in an immunity-dependent manner, and improve anti-tumor immunogenicity. USP8 inhibitor pretreatment led to reduced tumorigenesis and immunocompetent mice with Usp8 knockdown tumors exhibited extended survival. Moreover, USP8 interacted positively with PD-L1 and upregulated its expression by inhibiting the ubiquitination-regulated proteasome degradation pathway in pancreatic cancer. Combination therapy with a USP8 inhibitor and anti-PD-L1 effectively suppressed pancreatic tumor growth by activation of cytotoxic T-cells and the anti-tumor immunity was mainly dependent on the PD-L1 pathway and CD8 + T cells. Our findings highlight the importance of targeting USP8, which can sensitize PD-L1-targeted pancreatic cancer to immunotherapy and might represent a novel therapeutic strategy to treat patients with pancreatic tumors in the future.

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) serology in the vaccination era and post booster vaccination.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused over 6 million deaths world-wide. In the pre-vaccination era, we noted a 5·3% SARS-CoV-2 IgG antibody positivity rate in 81,624 subjects. Methods: Utilizing assays for serum SARS-CoV-2 spike (S) protein antibody (Roche) and neutralizing antibody (Diazyme), both >90% IgG, we measured antibodies in 13,189 subjects in the post-vaccination era, and in 69 subjects before and 60 days after booster vaccination. Results: In 2021, in 10,267 subjects, 25·0% had negative S protein levels (<0.80 U/L), 24·4% had low positive levels (0.80-250 U/L), and 50·7% had high positive levels (>250 U/L). Median neutralizing antibody levels were 1·16 and 2·06 AU/mL in the low and high positive groups, respectively. In 2022, we evaluated 2,016 subjects where samples were diluted 1:100 if S protein antibody levels were >250 U/L. Median S protein and neutralizing antibody levels were 2,065 U/L (86.3% positivity) and 2·68 AU/mL (68.0% positivity), respectively. Antibody levels were also measured in 69 subjects before and 60 days after receiving SARS-CoV-2 booster vaccinations. Treatment resulted in a 15-fold increase in S protein antibody levels from 1,010 to 17,236 U/L, and a 6-fold increase in neutralizing antibody from 1·51 to 12·51 AU/mL in neutralizing antibody levels, respectively (both P<0.00001), with a wide variability in response. Conclusions: Our data indicate that by early 2022 86% of subjects had positive SARS-CoV-2 S protein antibody levels, and that these levels and neutralizing antibody levels were increased 15-fold and 6-fold, respectively, 60 days after SARS-Cov-2 booster vaccination.

Fabrication of immobilized lipases for efficient preparation of 1,3-dioleoyl-2-palmitoylglycerol.

This study aims to fabricate immobilized lipases for efficient preparation of 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) through acidolysis of glycerol tripalmitate (PPP). Twelve (three types) supports and five lipases were studied carefully. Among them, the immobilized Thermomyces lanuginosa lipase (TLL) samples exhibited overall better performance than that of other immobilized lipases. Particularly, organic groups functionalized SBA-15 (R-SBA-15) supported TLL (TLL@R-SBA-15) samples gave PPP conversion from 97.70 to 99.00 % and OPO content from 59.52 to 64.73 %. After optimization, PPP conversion up to 99.07 %, OPO content 73.15 % and sn-2 palmitic acid content 90.09 % were obtained with TLL@C18H37-SBA-15 as catalyst. Moreover, TLL@C18H37-SBA-15 exhibited better acidolysis performance from 50 °C than that from 60 to 80 °C, which helped inhibit acyl migration. In addition, after 5 cycles of reuse, TLL@C18H37-SBA-15 retained 81.04 % (based on OPO content) and 98.88 % (based on sn-2 palmitic acid content) of its initial activity, indicating it had an attractive prospect in future applications.

Variability in the psychological impact of four waves of COVID-19: a time-series study of 60 000 text-based counseling sessions.

BACKGROUND: Continuous exposure to stressors can lead to vulnerability and, in some cases, resilience. This study examined the variation in its psychological impact across the first four waves of COVID-19 in Hong Kong. METHODS: Transcripts from Open Up, an online text-based counseling service, between January 2019 and January 2021 were analyzed (N = 60 775). We identified COVID-19 mentioned sessions using keywords and further categorized them into those that also mentioned symptoms of common mental disorders (CMDs) and those that did not. Autoregressive integrated moving average models were used to analyze the associations between the severity of the outbreak and the mention of COVID-19 and CMDs. RESULTS: Results revealed that the pandemic led to increased psychological distress. Compared to prior to its advent, more people sought help in the initial months of the outbreak. Furthermore, associations were found between the severity of the outbreak and the number of help-seeker mentioning the pandemic, as well as between the outbreak severity and the number of help-seekers disclosing psychological distress. However, these relationships were not uniform across the four waves of outbreaks; a dissociation between outbreak severity and help-seekers' concern was found in the fourth wave. CONCLUSION: As the pandemic waxes and wanes, people may become habituated to its psychological toll. This may be interpreted as a form of resilience. Instead of worsening with time, the psychological impact of COVID-19 may reduce with repeated exposure.

Curcumin loaded hydrogel with anti-inflammatory activity to promote cartilage regeneration in immunocompetent animals.

Stable cartilage regeneration in immunocompetent animals remains a huge challenge, mainly ascribing to the in vivo implantation of tissue-engineered cartilage inevitably arousing inflammatory reactions, resulting in cartilage-specific extracellular matrix erosion, chondrogenic niche destruction, and chondrocyte deterioration. Herein, we developed an anti-inflammatory platform, namely, Cur/GelMA hydrogel, by loading a potent anti-inflammatory drug of curcumin (Cur) into gelatin methacryloyl (GelMA) hydrogel. The Cur/GelMA hydrogel exhibited satisfactory Cur release kinetics in vitro and exerted favorable anti-inflammatory effects when cocultured with lipopolysaccharide-induced RAW264.7 macrophages in vitro. Furthermore, the Cur/GelMA hydrogel showed gratifying biocompatibility and supported cartilage regeneration in vitro when colonized with rabbit- and goat-derived chondrocytes. In addition, the in vitro engineered cartilages in the Cur/GelMA hydrogel were able to maintain a cartilaginous phenotype and achieved stable cartilage regeneration when subcutaneously implanted in autologous rabbits and goats for 2 and 4 weeks compared to the GelMA hydrogel. Furthermore, our data revealed that the in vivo-generated cartilage in the Cur/GelMA group apparently alleviated the inflammatory reaction compared to its GelMA counterpart, suggesting that the locally released Cur endowed the Cur/GelMA hydrogel with potent anti-inflammatory capacity. This study provides a reliable anti-inflammatory platform for stable cartilage regeneration in immunocompetent animals, significantly advancing the clinical application of tissue-engineered cartilage.

Network-based prediction of the disclosure of ideation about self-harm and suicide in online counseling sessions.

BACKGROUND: In psychological services, the transition to the disclosure of ideation about self-harm and suicide (ISS) is a critical point warranting attention. This study developed and tested a succinct descriptor to predict such transitions in an online synchronous text-based counseling service. METHOD: We analyzed two years' worth of counseling sessions (N = 49,770) from Open Up, a 24/7 service in Hong Kong. Sessions from Year 1 (N = 20,618) were used to construct a word affinity network (WAN), which depicts the semantic relationships between words. Sessions from Year 2 (N = 29,152), including 1168 with explicit ISS, were used to train and test the downstream ISS prediction model. We divided and classified these sessions into ISS blocks (ISSBs), blocks prior to ISSBs (PISSBs), and non-ISS blocks (NISSBs). To detect PISSB, we adopted complex network approaches to examine the distance among different types of blocks in WAN. RESULTS: Our analyses find that words within a block tend to form a module in WAN and that network-based distance between modules is a reliable indicator of PISSB. The proposed model yields a c-statistic of 0.79 in identifying PISSB. CONCLUSIONS: This simple yet robust network-based model could accurately predict the transition point of suicidal ideation prior to its explicit disclosure. It can potentially improve the preparedness and efficiency of help-providers in text-based counseling services for mitigating self-harm and suicide.

In online counseling, the help-provider can often be engaging with several service users simultaneously. Therefore, new tools that could help to alert and assist the help-provider and increase their preparedness for getting further help for service users could be useful. In this study, we developed and tested a new tool that is designed to alert help-providers to the disclosure of self-harm and suicidal thoughts, based on the words that the service user has been typing. The tool is developed on the basis that word usage may have a specific pattern when suicidal thoughts are more likely to occur. We tested our tool using two years' worth of online counseling conversations and we show that our approach can help to predict the confession of suicidal thoughts. As such, we are taking a step forward in helping to improve these counseling services.

Microbial Remediation of Crude Oil in Saline Conditions by Oil-Degrading Bacterium Priestia megaterium FDU301.

Salinity greatly affects the microbial degradation process of crude oil; thus, the isolation and identification of halotolerant microbes is essential. Limited studies explored how microbes respond to increased salinity. In this study, an oil-degrading bacterium Priestia megaterium FDU301 was isolated from the Dagang oil field, which can tolerate a salinity of 6%. Compared to the non-saline condition, oil degradation ratios by P. megaterium FDU301 increased by 15.27% and 11.26% in 0.5% and 3.5% salinity media, respectively. Meanwhile, bacteria degraded various components of crude oil more thoroughly in saline environments, especially mid-chain hydrocarbons (C11-C18). Surface tension under salt stress was lower than that in the non-saline medium, indicating that the amount of biosurfactants produced by bacteria was increased. The microbial activity enhanced markedly in response to increased salinity, which was the main factor for the high degradation ability. As a vital component of biofilms, the production of polysaccharides was accelerated with P. megaterium FDU301 inoculation in saline environments. These results indicate that P. megaterium FDU301 has great potential application in oil bioremediation in saline environments.

Renal-hepatic-pancreatic dysplasia-1 with a novel NPHP3 genotype: a case report and review of the literature.

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 1 (RHPD1) is a rare sporadic and autosomal recessive disorder with unknown incidence. RHPD1 is caused by biallelic pathogenic variants in NPHP3, which encode nephrocystin, an important component of the ciliary protein complex. CASE PRESENTATION: In this case report, we describe a male newborn who was confirmed by ultrasound to have renal enlargement with multiple cysts, pancreatic enlargement with cysts, and increased liver echogenicity, leading to the clinical diagnosis of RHPD. In addition, a compound heterozygous pathogenic variant, namely, NPHP3 c.1761G > A (p. W587*) and the c.69delC (p. Gly24Ala24*11) variant, was detected by WES. The patient was clinically and genetically diagnosed with RHPD1. At 34 h of life, the infant died of respiratory insufficiency. CONCLUSION: This is the first published case of RHPD1 in China. This study broadens the known range of RHPD1 due to NPHP3 pathogenic variants.