Zero-Strain Sodium Lanthanum Titanate Perovskite Embedded in Flexible Carbon Fibers as a Long-Span Anode for Lithium-Ion Batteries.

"High-capacity" graphite and "zero-strain" spinel Li4Ti5O12 (LTO) occupy the majority market of anode materials for Li+ storage in commercial applications. Nevertheless, their intrinsic drawbacks including the unsafe potential of graphite and unsatisfactory capacity of LTO limit the further development of lithium-ion batteries (LIBs), which is unable to satisfy the ever-increasing demands. Here, a novel Na0.35La0.55TiO3 perovskite embedded in multichannel carbon fibers (NLTO-NF) is rationally designed and synthesized through an electrospinning method. It not only has the advantages of a respectable specific capacity of 265 mAh g-1 at 0.1 A g-1 and superb rate capability, but it also possesses the zero-strain characteristic. Impressively, an ultralong cycling life with 96.3% capacity retention after 9000 cycles at 2 A g-1 is achieved in the half cell, and 90.3% of capacity retention ratio is obtained after even 2500 cycles at 1 A g-1 in the coupled LiFePO4/NLTO-NF full cell. This study introduces a new member with excellent performance to the zero-strain materials family for next-generation LIBs.

Hypophysitis Induced by Sintilimab in the Treatment of Bladder Cancer: A Case Report.

BACKGROUND: Immune checkpoint inhibitors (ICIs), as novel antitumor drugs, have been widely used in the clinic and have shown good antitumor effects. However, their widespread use has also led to the emergence of various immune-related adverse events (IrAEs). Hypophysitis is a rare but serious IrAE. Due to its complex and changeable clinical manifestations, hypophysitis may be easily overlooked, leading to delayed diagnosis and treatment. CASE PRESENTATION: A 68-year-old male patient was diagnosed with bladder cancer (T2bNXM0) in October 2021. He received two cycles of immunotherapy with sintilimab and chemotherapy with gemcitabine and cisplatin (GC). One month after the second treatment, he gradually developed recurrent fever, anorexia, drowsiness, and delirium. Laboratory examination revealed hyponatremia, decreased adrenocorticotropic hormone, and hypocortisolemia. The pituitary MRI showed no abnormality. The patient was diagnosed with immunotherapy-induced hypophysitis (IH) caused by sintilimab, leading to downstream endocrine disorders. With hormone replacement therapy, he was in a good mood, had a good appetite, and made an overall recovery. CONCLUSION: Immunotherapy-induced hypophysitis (IH) can result in a severe adrenal crisis, and prompt recognition and diagnosis are crucial. Clinicians must remain vigilant for the possibility of IH in patients who exhibit recurrent fever, anorexia, cognitive decline, and personality changes following ICI treatment. It is imperative to consider this diagnosis early to initiate appropriate management promptly.

Construction of "Coral" SERS sensor for ultrasensitive and rapid detection of harmful component macrophage migration inhibitory factor in Platelet-rich Plasma.

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory factor produced by residual red blood cell lysis, which can significantly influence the curative effect of Platelet-rich plasma (PRP) therapy used for osteoarthritis (OA) treatment. In this study, we proposed a novel approach for detecting the concentration of MIF in PRP using a dopamine-coated antibody-Au (core)-Ag (shell)-SERS sensor, which enables ultrasensitive and rapid detection of MIF. The best experimental conditions have a detection limit of only 90.05 pg/mL and a good linear relationship between 1-5000 ng/mL. In 40 PRP samples collected from actual clinical patients, we detected MIF concentrations ranging from 2.0-3.6 ng/mL. This indicated that the Coral SERS sensor not only allows for results highly consistent with the traditional ELISA method, but also costs less ($0.40-$0.70), needs shorter testing time (integration time is only 10s), and consumes less PRP that can greatly improve the sample quality and maximize the curative effect in clinical applications for OA treatment with PRP.

RNautophagic regulation of DNMT3a-dependent DNA methylation by Linc00942 enhances chemoresistance in gastric cancer.

BACKGROUND: Energy balance has long been known to extend lifespans and inhibit carcinogenesis in multiple species by slowing age-related epigenetic changes while the underlying mechanisms remain largely unknown. Herein, we found that starvation activated autophagy to remodel the DNA methylation profile by inhibiting DNMT3a expression. METHODS: Illumina Infinium MethylationEPIC BeadChip and dot blot assay were performed to quantify the global DNA methylation level. Protein-RNA interactions were validated through RNA immunoprecipitation and RNA pull-down assay. In vitro and in vivo experiments were carried out to testify the effect of DNMT3a on chemoresistance. RESULTS: Autophagy is impaired in chemoresistance which was associated with differential DNA methylation and could be reversed by DNMT3a inhibition. Autophagy activation decreases the expression of DNMT3a mRNA, accompanied with the downregulation of chemoresistance-related Linc00942. Knockdown of Linc00942 reduces DNMT3a expression and genome-wide DNA methylation while Linc00942 overexpression increased DNMT3a expression and correlated hypermethylation in cancer cells and primary tumour tissues. Mechanistically, Linc00942 recruits RNA methyltransferase METTL3 to stimulate N6-methyladenosine (m6A) deposit on DNMT3a transcripts, triggering IGF2BP3/HuR to recognize modified mRNA for reinforced stability. SQSTM1/p62 recruits Linc00942 for autophagic degradation which can be abrogated after autophagy inhibition by p62 knockdown or chloroquine treatment. CONCLUSIONS: Inhibition of autophagy increases Linc00942 expression to promote chemoresistance and autophagy activation or hypomethylating agent decitabine restores chemosensitivity by reducing global DNA methylation. Overall, this study identifies a novel methylation cascade linking impaired RNautophagy to global hypermethylation in chemoresistance, and provides a rationale for repurposing decitabine to overcome chemoresistance in cancer treatment.

Fine valence regulation of hydrated vanadium oxide as a novel cathode for stable potassium-ion storage.

Layered V10O24·nH2O with a large interlayer spacing of 14 Å is hydrothermally synthesized and used as a cathode for potassium-ion batteries. It exhibits a capacity of 110 mA h g-1 with a capacity retention of 99.2% over 700 cycles. Its storage mechanism is identified as pseudo-capacitive intercalation.

A Novel Defined PANoptosis-Related miRNA Signature for Predicting the Prognosis and Immune Characteristics in Clear Cell Renal Cell Carcinoma: A miRNA Signature for the Prognosis of ccRCC.

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent cancers, and PANoptosis is a distinct, inflammatory-programmed cell death regulated by the PANoptosome. The essential regulators of cancer occurrence and progression are microRNAs (miRNAs). However, the potential function of PANoptosis-related microRNAs (PRMs) in ccRCC remains obscure. This study retrieved ccRCC samples from The Cancer Genome Atlas database and three Gene Expression Omnibus datasets. PRMs were recognized based on previous reports in the scientific literature. Regression analyses were used to identify the prognosis PRMs and construct a PANoptosis-related miRNA prognostic signature based on the risk score. We discovered that high-risk patients had poorer survival prognoses and were significantly linked to high-grade and advanced-stage tumors, using a variety of R software packages and web analysis tools. Furthermore, we demonstrated that the low-risk group had significant changes in their metabolic pathways. In contrast, the high-risk group was characterized by high immune cell infiltration, immune checkpoint expression, and low half-maximum inhibition concentration (IC50) values of chemotherapeutic agents. This suggests that high-risk patients may benefit more from immunotherapy and chemotherapy. In conclusion, we constructed a PANoptosis-related microRNA signature and revealed its potential significance in clinicopathological features and tumor immunity, thereby providing new precise treatment strategies.

Investigating the effectiveness of electronically delivered cognitive behavioural therapy (e-CBTi) compared to pharmaceutical interventions in treating insomnia: Protocol for a randomized controlled trial.

BACKGROUND: Insomnia is one of the most prevalent sleep disorders characterized by an inability to fall or stay asleep. Available treatments include pharmacotherapy and cognitive behavioural therapy for insomnia (CBTi). Although CBTi is the first-line treatment, it has limited availability. Therapist-guided electronic delivery of CBT for insomnia (e-CBTi) offers scalable solutions to enhance access to CBTi. While e-CBTi produces comparable outcomes to in-person CBTi, there is a lack of comparison to active pharmacotherapies. Therefore, direct comparisons between e-CBTi and trazodone, one of the most frequently prescribed medications for insomnia, is essential in establishing the effectiveness of this novel digital therapy in the health care system. OBJECTIVE: The aim of this study is to compare the effectiveness of a therapist-guided electronically-delivered cognitive behavioural therapy (e-CBTi) program to trazodone in patients with insomnia. METHODS: Patients (n = 60) will be randomly assigned to two groups: treatment as usual (TAU) + trazodone and TAU + e-CBTi for seven weeks. Each weekly sleep module will be delivered through the Online Psychotherapy Tool (OPTT), a secure, online mental health care delivery platform. Changes in insomnia symptoms will be evaluated throughout the study using clinically validated symptomatology questionnaires, Fitbits, and other behavioural variables. RESULTS: Participant recruitment began in November 2021. To date, 18 participants have been recruited. Data collection is expected to conclude by December 2022 and analyses are expected to be completed by January 2023. CONCLUSIONS: This comparative study will improve our understanding of the efficacy of therapist-guided e-CBTi in managing insomnia. These findings can be used to develop more accessible and effective treatment options and influence clinical practices for insomnia to further expand mental health care capacity in this population. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05125146).

HSF1 promotes CD69+ Treg differentiation to inhibit colitis progression.

Regulatory T cells (Tregs) are critical for generating and maintaining peripheral tolerance. Treg-based immunotherapy is valuable for the clinical management of diseases resulting from dysregulation of immune tolerance. However, the lack of potency is a potential limitation of Treg therapy. In addition, CD69 positive-Treg (CD69+ Treg) represent a newly identified subset of Tregs with potent immune suppressive capability. Methods: Foxp3 YFP-Cre CD69 fl/fl and CD4 Cre CD69 fl/fl mice were generated to determine the relevance of CD69 to Treg. Chromatin Immunoprecipitation Assay (ChIP) and luciferase Assay were performed to detect the regulation of CD69 transcription by heat shock transcription factor 1(HSF1). Gene expression was measured by western blotting and qRT-PCR. The differentiation of naive T cells to CD69+Foxp3+ iTregs was determined by flow cytometry. The immunosuppressive ability of Tregs was analyzed by ELISA and flow cytometry. Colon inflammation in mice was reflected by changes in body weight and colon length, the disease activity index (DAI), and H&E staining of colon tissues. Results: Induced Tregs (iTregs) from CD4 Cre CD69 fl/fl mice failed to alleviate colitis. The transcription factor HSF1 interacted with the promoter of the CD69 gene to prompt its transcription during Treg differentiation. Genetic and chemical inhibition of HSF1 impaired CD69+ Treg differentiation and promoted the pathogenesis of colitis in mice. In contrast, HSF1 protein stabilized by inhibiting its proteasomal degradation promoted CD69+ Treg differentiation and alleviated colitis in mice. Moreover, adoptive transfer of iTregs with HSF1 stabilization by proteasome inhibitor (PSI) dramatically prevented the development of colitis in mice and was accompanied by decreased production of pro-inflammatory cytokines and reduced accumulation of pro-inflammatory lymphocytes in colitis tissue, whereas Tregs induced in the absence of PSI were less stable and ineffective in suppressing colitis. Conclusions: HSF1 promotes CD69+ Tregs differentiation by activating the CD69 transcription, which is critical for the immunosuppressive function of Tregs. Stabilization of HSF1 by PSIs results in the efficient generation of Tregs with high potency to treat colitis and probably other autoimmune diseases involving Tregs deficiency.

Adjustable-Loop Cortical Button Fixation Results in Good Clinical Outcomes for Acute Tibial Avulsion Fracture of the Posterior Cruciate Ligament.

Purpose: To evaluate the clinical outcomes for arthroscopic treatment of acute posterior cruciate ligament (PCL) avulsion fractures with adjustable-loop cortical button fixation device. Methods: Patients with PCL tibial avulsion fractures treated with an adjustable-loop cortical button fixation device between October 2019 and October 2020 were retrospectively identified. Patients with type 1 were treated using plaster fixation as a conservative treatment, whereas patients with type 2 and 3 with displacement were treated using an arthroscopic adjustable-loop cortical button. Operating time, incision recovery, complications, and postoperative fracture healing time were monitored. All patient follow-up was done at 12 months' postoperatively. Lysholm Knee Score and the International Knee Documentation Committee score were used to assess knee function. Results: A total of 30 patients were included in the study (20 male/10 female; mean age 45.5 years, range 35-68 years). The mean operative time was 67.5 minutes (range: 50-90 minutes). The postoperative incision healed at stage A without complications, such as medically induced vascular nerve injury, intra-articular hematoma, or infection. All 30 patients were tracked postoperatively for 12 to 14 months, with a mean follow-up period of 12.6 months. The Lysholm knee function score was 45.93 ± 6.15 before surgery and 87.10 ± 3.71 at 12 months after surgery, and the International Knee Documentation Committee score was 19.27 ± 4.40 before surgery and 95.47 ± 1.87 at 12 months after surgery, with a statistically significant difference. Conclusions: The treatment of PCL avulsion fractures with arthroscopic adjustable-loop cortical button fixation is easy to perform and shows good clinical results in our study. Level of Evidence: IV, therapeutic case series.

2-Aminopyrimidine derivatives as selective dual inhibitors of JAK2 and FLT3 for the treatment of acute myeloid leukemia.

Dual inhibitors of JAK2 and FLT3 can synergistically control the development of acute myeloid leukemia (AML), and overcome secondary drug resistance of AML that is associated with FLT3 inhibition. We therefore designed and synthesized a series of 4-piperazinyl-2-aminopyrimidines as dual inhibitors of JAK2 and FLT3, and improved their selectivity for JAK2. Screening cascades revealed that compound 11r exhibited inhibitory activity with IC50 values of 2.01, 0.51, and 104.40 nM against JAK2, FLT3, and JAK3, respectively. Compound 11r achieved a high selectivity for JAK2 at a ratio of 51.94, and also showed potent antiproliferative activity in HEL (IC50 = 1.10 µM) and MV4-11 (IC50 = 9.43 nM) cell lines. In an in vitro metabolism assay, 11r exhibited moderate stability in human liver microsomes (HLMs), with a half-life time of 44.4 min, and in rat liver microsomes (RLMs), with a half-life of 143 min. In pharmacokinetic studies, compound 11r showed moderate absorption (Tmax = 5.33 h), with a peak concentration of 38.7 ng/mL and an AUC of 522 ng h/mL in rats, and an oral bioavailability of 25.2%. In addition, 11r induced MV4-11 cell apoptosis in a dose-dependent manner. These results indicate that 11r is a promising selective JAK2/FLT3 dual inhibitor.

A genome-wide cross-cancer meta-analysis highlights the shared genetic links of five solid cancers.

Breast, ovarian, prostate, lung, and head/neck cancers are five solid cancers with complex interrelationships. However, the shared genetic factors of the five cancers were often revealed either by the combination of individual genome-wide association study (GWAS) approach or by the fixed-effect model-based meta-analysis approach with practically impossible assumptions. Here, we presented a random-effect model-based cross-cancer meta-analysis framework for identifying the genetic variants jointly influencing the five solid cancers. A comprehensive genetic correlation analysis (genome-wide, partitioned, and local) approach was performed by using GWAS summary statistics of the five cancers, and we observed three cancer pairs with significant genetic correlation: breast-ovarian cancer (r g = 0.221, p = 0.0003), breast-lung cancer (r g = 0.234, p = 7.6 × 10-6), and lung-head/neck cancer (r g = 0.652, p = 0.010). Furthermore, a random-effect model-based cross-trait meta-analysis was conducted for each significant cancer pair, and we found 27 shared genetic loci between breast and ovarian cancers, 18 loci between breast and lung cancers, and three loci between lung and head/neck cancers. Functional analysis indicates that the shared genes are enriched in human T-cell leukemia virus 1 infection (HTLV-1) and antigen processing and presentation (APP) pathways. Our study investigates the shared genetic links across five solid cancers and will help to reveal their potential molecular mechanisms.

A qualitative exploration of the mental health challenges and therapeutic needs of Canadian correctional workers.

Purpose: Correctional work is described as a high-stress environment associated with increased prevalence of mental health disorders in employees. Identifying appropriate healthcare services necessitates investigating the mental health challenges and needs of correctional workers (CWs). Methods: Individual interviews (n = 9; 5 M and 4 W) and a mixed gender focus group (n = 6; 3 M and 3 W) were conducted to gather a general sense of the mental health landscape. Data were analyzed to develop a targeted and comprehensive question guide for gender-specific focus groups (n = 14 unique participants; 6 M and 8 W). Results: Eight themes emerged from the gender-specific focus groups. Themes focusing on work culture described the negative repercussions of job stress and the inability to discuss challenges openly due to confidentiality concerns and feelings of seclusion associated with the CW profession. Men were more likely to be subjected to physical violence and women to emotional and sexual harassment from staff and inmates. Themes related to mental health care described the benefits and limitations of the current services and digital mental healthcare. Stigma and accessibility were notable treatment barriers. Lastly, sector-specific therapy was seen as an important component in enhancing engagement and therapist interaction. Conclusion: The study demonstrates the interconnection between work culture and CW mental health that needs to be acknowledged when addressing mental health care.

RNA-based therapeutics: an overview and prospectus.

The growing understanding of RNA functions and their crucial roles in diseases promotes the application of various RNAs to selectively function on hitherto "undruggable" proteins, transcripts and genes, thus potentially broadening the therapeutic targets. Several RNA-based medications have been approved for clinical use, while others are still under investigation or preclinical trials. Various techniques have been explored to promote RNA intracellular trafficking and metabolic stability, despite significant challenges in developing RNA-based therapeutics. In this review, the mechanisms of action, challenges, solutions, and clinical application of RNA-based therapeutics have been comprehensively summarized.

Therapeutic Effects of Curcumin on Osteoarthritis and Its Protection of Chondrocytes Through the Wnt/Β-Catenin Signaling Pathway.

Context: Osteoarthritis (OA) is a high-incidence, chronic condition, with an extremely high prevalence among older adults. OA seriously compromises the normal living of OA patients, and it's imperative to find a novel therapy as soon as possible to improve their prognosis and life quality. Objective: The study intended to investigate the therapeutic effects of Curcumin (Cur) on OA and to explore its preliminary mechanism of action, with the aim of offering more accurate guidance for use of OA therapy. Design: The research team designed a prospective non-randomized controlled trial. Setting: The study took place in the Department of Orthopedics at Sir Run Run Hospital at Nanjing Medical University in Nanjing, China. Participants: Participants were 107 OA patients treated at the hospital between March 2019 and January 2020. Intervention: Participants were divided into two groups, 51 in the Cur group and 56 in the ibuprofen group. Outcome Measures: The clinical efficacy and safety of the two groups were observed. In addition, the research team performed in-vitro studies. Chondrocytes HC-a and C28/I2 were purchased to evaluate the intracellular inflammatory response and apoptosis rate under the intervention of Cur and Wnt/ß-catenin pathway inhibitors. Results: No significant differences existed in the clinical-efficacy rate between the two groups (P > .05), but the Cur group show higher improvements in safety, joint mobility, and inhibition of inflammation (P < .05). In-vitro experiments showed that Cur inhibited the apoptosis rate of chondrocytes and the levels of inflammatory factors, while the Wnt/ß-catenin inhibitor did the opposite (P < .05). Conclusions: Cur can effectively decrease the pathological results of OA, with a remarkable safety profile; its mechanism may be the activation of the Wnt/ß-catenin signaling pathway to inhibit the inflammatory reaction and apoptosis in chondrocytes.

Co-targeting WIP1 and PARP induces synthetic lethality in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most fatal cancers. Due to limited strategies for effective treatments, patients with advanced HCC have a very poor prognosis. This study aims to identify new insights in HCC to develop novel strategies for HCC management. METHODS: The role of WIP1 (wild type p53 induced protein phosphatase1) in HCC was analyzed in HCC cells, xenograft model, DEN (Diethylnitrosamine) induced mice liver cancer model with WIP1 knockout mice, and TCGA database. DNA damage was evaluated by Gene Set Enrichment Analysis, western blotting, comet assay, and Immunofluorescence. RESULTS: High expression of WIP1 is associated with the poor prognosis of patients with HCC. Genetically and chemically suppression of WIP1 drastically reduced HCC cell proliferation. Besides, WIP1 knockout retarded DEN induced mice hepato-carcinogenesis. Mechanically, WIP1 inhibition induced DNA damage by increasing H2AX phosphorylation (γH2AX). Therefore, suppression of WIP1 and PARP induced synthetic lethality in HCC in vitro and in vivo by augmenting DNA damage. CONCLUSION: WIP1 plays an oncogenic effect in HCC development, and targeting WIP1-dependent DNA damage repair alone or in combination with PARP inhibition might be a reasonable strategy for HCC management. Video abstract.

LncRNA LINC00942 promotes chemoresistance in gastric cancer by suppressing MSI2 degradation to enhance c-Myc mRNA stability.

BACKGROUND: Chemoresistance to cisplatin (DDP) remains a major challenge in advanced gastric cancer (GC) treatment. Although accumulating evidence suggests an association between dysregulation of long non-coding RNAs (lncRNAs) and chemoresistance, the regulatory functions and complexities of lncRNAs in modulating DDP-based chemotherapy in GC remain under-investigated. This study was designed to explore the critical chemoresistance-related lncRNAs in GC and identify novel therapeutic targets for patients with chemoresistant GC. METHODS: Chemoresistance-related lncRNAs were identified through microarray and verified through a quantitative real-time polymerase chain reaction (qRT-PCR). Proteins bound by lncRNAs were identified through a human proteome array and validated through RNA immunoprecipitation (RIP) and RNA pull-down assays. Co-immunoprecipitation and ubiquitination assays were performed to explore the molecular mechanisms of the Musashi2 (MSI2) post-modification. The effects of LINC00942 (LNC942) and MSI2 on DDP-based chemotherapy were investigated through MTS, apoptosis assays and xenograft tumour formation in vivo. RESULTS: LNC942 was found to be up-regulated in chemoresistant GC cells, and its high expression was positively correlated with the poor prognosis of patients with GC. Functional studies indicated that LNC942 confers chemoresistance to GC cells by impairing apoptosis and inducing stemness. Mechanically, LNC942 up-regulated the MSI2 expression by preventing its interaction with SCFß-TRCP E3 ubiquitin ligase, eventually inhibiting ubiquitination. Then, LNC942 stabilized c-Myc mRNA in an N6-methyladenosine (m6 A)-dependent manner. As a potential m6 A recognition protein, MSI2 stabilized c-Myc mRNA with m6 A modifications. Moreover, inhibition of the LNC942-MSI2-c-Myc axis was found to restore chemosensitivity both in vitro and in vivo. CONCLUSIONS: These results uncover a chemoresistant accelerating function of LNC942 in GC, and disrupting the LNC942-MSI2-c-Myc axis could be a novel therapeutic strategy for GC patients undergoing chemoresistance.

Changes in the bacterial communities in chromium-contaminated soils.

Introduction: Hexavalent chromium or Cr(VI) is essential to various industries, such as leather manufacturing and stainless steel production. Given that inevitable leakage from industries pollutes the soil and thereby affects the soil environment. Microbial communities could improve the quality of the soil. Abundant bacterial communities would significantly enhance the soil richness and resist external pressure, benefiting agriculture. But the pollution of heavy metal broke the balance and decrease the abundance of bacterial communities, which weak the self-adjust ability of soil. This study aimed to explore changes in the diversity of soil bacterial communities and to identify the influences of soil bacterial communities on enzymes in soil polluted by Cr(VI). Methods: The target soils were sampled quickly and aseptically. Their chromium content was detected through inductively coupled plasma-mass spectrometry, and bacterial microbiome communities were explored through MiSeq high-throughput sequencing. Then, the content of nitrite reductase and catalases were investigated through enzyme-linked immunosorbent assay (ELISA). Results: Chromium content in polluted soils was higher than that in the control soils at all depths. Sobs, Chao1, Ace, and Shannon diversity estimators in the control were higher, whereas Simpson's diversity estimators in the control soils were lower than those of contaminated samples at all depths. Contaminants affected the composition of the bacterial community. The soil microbial species were relatively single and inhomogeneous in the polluted soils. The bacterial phyla in polluted and controlled soils include Proteobacteria, Actinobacteria, Chloroflexi, and Acidobacteria, which differ markedly in abundance. Discussion: The results of these observations provide insights into the ecotoxicological effects of Cr(VI) exposure to soil microorganisms. To sum up these results are critical for evaluating the stabilized state of microbial community structures, contributing to the assessment of the potential risk of metal accumulation in soils.

Transcriptomic Characterization of the Effects of Selenium on Maize Seedling Growth.

Selenium (Se) is a trace mineral element in soils that can be beneficial to plants in small amounts. Although maize is among the most economically important crops, there are few reports on the effects of Se on maize seedling growth at the molecular level. In this study, the growth of maize seedlings treated with different concentrations of Na2SeO3 was investigated, and the physiological characteristics were measured. Compared with the control, a low Se concentration promoted seedling growth, whereas a high Se concentration inhibited it. To illustrate the transcriptional effects of Se on maize seedling growth, samples from control plants and those treated with low or high concentrations of Se were subjected to RNA sequencing. The differentially expressed gene (DEG) analysis revealed that there were 239 upregulated and 106 downregulated genes in the low Se treatment groups, while there were 845 upregulated and 1,686 downregulated DEGs in the high Se treatment groups. Both the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses showed a low concentration of the Se-stimulated expression of "DNA replication" and "glutathione (GSH) metabolism"-related genes. A high concentration of Se repressed the expression of auxin signal transduction and lignin biosynthesis-related genes. The real-time quantitative reverse transcription PCR (qRT-PCR) results showed that in the low Se treatment, "auxin signal transduction," "DNA replication," and lignin biosynthesis-related genes were upregulated 1.4- to 57.68-fold compared to the control, while, in the high Se concentration treatment, auxin signal transduction and lignin biosynthesis-related genes were downregulated 1.6- to 16.23-fold compared to the control. Based on these transcriptional differences and qRT-PCR validation, it was found that a low dosage of Se may promote maize seedling growth but becomes inhibitory to growth at higher concentrations. This study lays a foundation for the mechanisms underlying the effects of Se on maize seedling growth.

Targeting ATF4-dependent pro-survival autophagy to synergize glutaminolysis inhibition.

As glutamine plays a central role in cancer metabolism, inhibition of glutaminolysis has become an ideal anticancer therapeutic target. However, glutaminolysis inhibition leads to activation of autophagy, which compromises its antitumor effect. Hence, we investigated the mechanism underlying glutaminolysis inhibition-induced pro-survival autophagy. Methods: High-throughput sequencing was performed on colorectal cancer (CRC) cells before and after glutaminolysis inhibition to identify differentially expressed genes. Activating transcription factor 4 (ATF4) pathway enrichment in glutaminolysis inhibited cells was identified through gene set enrichment analysis. ATF4 expression was assessed by quantitative real-time PCR (qRT-PCR) and western blotting. The function of ATF4 on mechanistic target of rapamycin (mTOR) regulation was assessed by western blotting. Luciferase reporter assays and chromatin immunoprecipitation were used to confirm the regulation of DNA damage inducible transcript 4 (DDIT4) by ATF4. mRNA half-life assays, RNA immunoprecipitation, qRT-PCR and western blotting were performed to determine the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 regulation of pro-survival autophagy was measured by tandem monomeric red fluorescent protein-green fluorescent protein fluorescence microscopy. Finally, the synergistic effect of autophagy and glutaminolysis inhibition was analyzed in an azoxymethane/dextran sodium sulfate mouse model. Results: The ATF4 pathway was activated in CRC cells upon glutaminolysis inhibition. Functionally, ATF4 transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition. Interestingly, glutaminolysis inhibition promoted ATF4 mRNA expression by abrogating N6-methyladenosine (m6A) modification and YTHDF2-mediated RNA decay. Finally, inhibition of ATF4-induced autophagy enhanced the antitumor efficacy of glutaminolysis inhibition. Conclusion: Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Targeting ATF4-induced autophagy is a new strategy to synergize glutaminolysis-targeting therapies for cancer treatment.

Delivering an Online Cognitive Behavioral Therapy Program to Address Mental Health Challenges Faced by Correctional Workers and Other Public Safety Personnel: Protocol for a Mixed Methods Study.

BACKGROUND: Public safety personnel have regular and often intense exposure to potentially traumatic events at work, especially workplace violence in the case of correctional workers. Subsequently, correctional workers are at higher risk of developing mental health problems such as posttraumatic stress disorder. Public safety personnel are up to 4 times more likely to experience suicidal ideation, suicidal attempts, and death by suicide compared to the general population. Despite this high prevalence, help-seeking behaviors from public safety personnel are low due to stigma and irregular work hours limiting access to care. Innovative treatments are needed to address these challenges. OBJECTIVE: This study will investigate the efficacy of an electronically delivered cognitive behavioral therapy (e-CBT) program tailored to correctional workers' mental health problems. METHODS: This study is composed of 4 phases. In phase 1, we will interview correctional workers individually and in focus groups to identify personal, social, and cultural factors affecting their mental health and barriers to care. Phase 2 will use the information gathered from the interviews to develop gender- and diagnosis-specific e-CBT modules. These will be presented to a new group of participants who will provide further feedback on their usability and accessibility. In phase 3, we will randomly assign participants to either an e-CBT or treatment as usual arm. The program will be evaluated with validated symptomatology questionnaires and interviews. Phase 4 will use this additional information to fine-tune the e-CBT modules for a larger-scale randomized controlled trial design comparing the e-CBT program to in-person CBT. All e-CBT modules will be delivered through a secure online platform. RESULTS: The study received ethics approval in December 2020, and participant recruitment began in March 2021. Participant recruitment has been conducted through targeted advertisements and physician referrals. To date, there have been 15 participants recruited for Phase 1, and it is expected to conclude in July 2021, with phase 2 beginning in September 2021. Complete data collection and analysis from all phases are expected to conclude by July 2023. Linear and binomial regression (for continuous and categorical outcomes, respectively) will be conducted along with interpretive qualitative methods. CONCLUSIONS: If proven efficacious and feasible, this e-CBT program can provide a high-quality and clinically validated resource to address the mental health problems of correctional workers. Additionally, findings can contribute to the development of innovative treatments for other public safety professions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04666974; https://www.clinicaltrials.gov/ct2/show/NCT04666974. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30845.