Comparison between intramedullary nail and conventional plate for displaced intra-articular calcaneal fractures: A meta-analysis.

OBJECTIVES: This study aimed to compare the efficacy and safety of the intramedullary nail and conventional plate for the treatment of displaced intra-articular calcaneal fractures from clinical comparative trials. MATERIALS AND METHODS: A comprehensive search of English databases was carried out in the Springer, PubMed, ScienceDirect, Web of Science, and Cochrane Library databases until September 2023. Studies on calcaneal fractures treated by an intramedullary nail or a plate were considered for inclusion. Endpoints included duration of operation, length of hospital stay, the Visual Analog Scale (VAS) score, postoperative functional score, radiological parameters, and complications. The mean difference (MD) and risk difference (RD) as the combined variables, as well as the 95% confidence intervals, (CIs) were calculated. RESULTS: Five retrospective controlled studies covering 473 feet at the one-year follow-up met the inclusion criteria. The meta-analysis demonstrated that there were significant differences in the duration of operation (MD: -10.81; 95% CI: -16.32, -5.31; p=0.0001), length of hospital stay (MD: -3.65; 95% CI: -4.35, -2.95; p<0.00001). No significant differences were found regarding postoperative American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale (MD: 0.36; 95% CI: -3.89, 4.61; p=0.87), VAS (MD: 1.95; 95% CI: -0.30, 4.21; p=0.09), or postoperative Böhler angle (MD: 0.94; 95% CI: -0.04, 1.92; p=0.06) between the two groups. The incidence of total complications (RD: -0.31; 95% CI: -0.46, -0.17; p<0.0001) and wound-healing complications (RD: -0.16; 95% CI: -0.30, -0.03; p=0.02) were lower in the intramedullary nail group. There were no significant differences in the incidences of revision surgery, implant removal, superficial wound infection, deep infection, and nonunion. CONCLUSION: Compared to conventional plates, the intramedullary nail showed a shorter duration of operation, reduced length of hospital stay, and fewer postoperative total complications and wound-healing complications in treating displaced intra-articular calcaneal fractures.

Stanniocalcin 2 governs cancer cell adaptation to nutrient insufficiency through alleviation of oxidative stress.

Solid tumours often endure nutrient insufficiency during progression. How tumour cells adapt to temporal and spatial nutrient insufficiency remains unclear. We previously identified STC2 as one of the most upregulated genes in cells exposed to nutrient insufficiency by transcriptome screening, indicating the potential of STC2 in cellular adaptation to nutrient insufficiency. However, the molecular mechanisms underlying STC2 induction by nutrient insufficiency and subsequent adaptation remain elusive. Here, we report that STC2 protein is dramatically increased and secreted into the culture media by Gln-/Glc-deprivation. STC2 promoter contains cis-elements that are activated by ATF4 and p65/RelA, two transcription factors activated by a variety of cellular stress. Biologically, STC2 induction and secretion promote cell survival but attenuate cell proliferation during nutrient insufficiency, thus switching the priority of cancer cells from proliferation to survival. Loss of STC2 impairs tumour growth by inducing both apoptosis and necrosis in mouse xenografts. Mechanistically, under nutrient insufficient conditions, cells have increased levels of reactive oxygen species (ROS), and lack of STC2 further elevates ROS levels that lead to increased apoptosis. RNA-Seq analyses reveal STC2 induction suppresses the expression of monoamine oxidase B (MAOB), a mitochondrial membrane enzyme that produces ROS. Moreover, a negative correlation between STC2 and MAOB levels is also identified in human tumour samples. Importantly, the administration of recombinant STC2 to the culture media effectively suppresses MAOB expression as well as apoptosis, suggesting STC2 functions in an autocrine/paracrine manner. Taken together, our findings indicate that nutrient insufficiency induces STC2 expression, which in turn governs the adaptation of cancer cells to nutrient insufficiency through the maintenance of redox homeostasis, highlighting the potential of STC2 as a therapeutic target for cancer treatment.

Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial.

We report the results of 24 women, 50% (N = 12) with hormone receptor-positive breast cancer and 50% (N = 12) with advanced triple-negative breast cancer, treated with entinostat + nivolumab + ipilimumab from the dose escalation (N = 6) and expansion cohort (N = 18) of ETCTN-9844 ( NCT02453620 ). The primary endpoint was safety. Secondary endpoints were overall response rate, clinical benefit rate, progression-free survival and change in tumor CD8:FoxP3 ratio. There were no dose-limiting toxicities. Among evaluable participants (N = 20), the overall response rate was 25% (N = 5), with 40% (N = 4) in triple-negative breast cancer and 10% (N = 1) in hormone receptor-positive breast cancer. The clinical benefit rate was 40% (N = 8), and progression-free survival at 6 months was 50%. Exploratory analyses revealed that changes in myeloid cells may contribute to responses; however, no correlation was noted between changes in CD8:FoxP3 ratio, PD-L1 status and tumor mutational burden and response. These findings support further investigation of this treatment in a phase II trial.

A cyclin D1 intrinsically disordered domain accesses modified histone motifs to govern gene transcription.

The essential G1-cyclin, CCND1, is frequently overexpressed in cancer, contributing to tumorigenesis by driving cell-cycle progression. D-type cyclins are rate-limiting regulators of G1-S progression in mammalian cells via their ability to bind and activate CDK4 and CDK6. In addition, cyclin D1 conveys kinase-independent transcriptional functions of cyclin D1. Here we report that cyclin D1 associates with H2BS14 via an intrinsically disordered domain (IDD). The same region of cyclin D1 was necessary for the induction of aneuploidy, induction of the DNA damage response, cyclin D1-mediated recruitment into chromatin, and CIN gene transcription. In response to DNA damage H2BS14 phosphorylation occurs, resulting in co-localization with γH2AX in DNA damage foci. Cyclin D1 ChIP seq and γH2AX ChIP seq revealed ~14% overlap. As the cyclin D1 IDD functioned independently of the CDK activity to drive CIN, the IDD domain may provide a rationale new target to complement CDK-extinction strategies.

GATA-3-dependent Gene Transcription is Impaired upon HDAC Inhibition.

PURPOSE: Many peripheral and cutaneous T-cell lymphoma (CTCL) subtypes are poorly responsive to conventional chemotherapeutic agents and associated with dismal outcomes. The zinc finger transcription factor GATA-3 and the transcriptional program it instigates are oncogenic and highly expressed in various T-cell neoplasms. Posttranslational acetylation regulates GATA-3 DNA binding and target gene expression. Given the widespread use of histone deacetylase inhibitors (HDACi) in relapsed/refractory CTCL, we sought to examine the extent to which these agents attenuate the transcriptional landscape in these lymphomas. EXPERIMENTAL DESIGN: Integrated GATA-3 chromatin immunoprecipitation sequencing and RNA sequencing analyses were performed in complementary cell line models and primary CTCL specimens treated with clinically available HDACi. RESULTS: We observed that exposure to clinically available HDACi led to significant transcriptional reprogramming and increased GATA-3 acetylation. HDACi-dependent GATA-3 acetylation significantly impaired both its ability to bind DNA and transcriptionally regulate its target genes, thus leading to significant transcriptional reprogramming in HDACi-treated CTCL. CONCLUSIONS: Beyond shedding new light on the mechanism of action associated with HDACi in CTCL, these findings have significant implications for their use, both as single agents and in combination with other novel agents, in GATA-3-driven lymphoproliferative neoplasms.

Molecular Targets and Mechanisms of Hedyotis diffusa Willd. for Esophageal Adenocarcinoma Treatment Based on Network Pharmacology and Weighted Gene Co-expression Network Analysis.

BACKGROUND: Hedyotis diffusa Willd. (HDW) is a common anticancer herbal medicine in China, and its therapeutic effectiveness has been demonstrated in a range of cancer patients. There is no consensus about the therapeutic targets and molecular mechanisms of HDW, which contains many active ingredients. AIM: To clarify the mechanism of HDW for esophageal adenocarcinoma (EAC), we utilized network pharmacology and weighted gene co-expression network analysis methods (WGCNA). METHODS: The gene modules that were linked with the clinical features of EAC were obtained through the WGCNA method. Then, the potential target genes were retrieved through the network pharmacology method in order to determine the targets of the active components. After enrichment analysis, a variety of signaling pathways with significant ratios of target genes were found, including regulation of trans-synaptic signaling, neuroactive ligand-receptor interaction and modulation of chemical synaptic transmission. By means of protein-protein interaction (PPI) network analysis, we have successfully identified the hub genes, which were AR, CNR1, GRIK1, MAPK10, MAPT, PGR and PIK3R1. RESULT: Our study employed molecular docking simulations to evaluate the binding affinity of the active components with the hub gene. The identified active anticancer constituents in HDW are scopoletol, quercetin, ferulic acid, coumarin, and trans-4-methoxycinnamyl alcohol. CONCLUSION: Our findings shed light on the molecular underpinnings of HDW in the treatment of EAC and hold great promise for the identification of potential HDW compounds and biomarkers for EAC therapy.

Abnormal preoperative fMRI signal variability in the pain ascending pathway is associated with the postoperative axial pain intensity in degenerative cervical myelopathy patients.

BACKGROUND CONTEXT: The moment-to-moment variability of resting-state brain activity has been suggested to play an active role in chronic pain. PURPOSE: To investigate preoperative alterations in regional blood-oxygen-level-dependent signal variability (BOLDsv) and inter-regional dynamic functional connectivity (dFC) in individuals with degenerative cervical myelopathy (DCM), and their potential association with postoperative axial pain severity. STUDY DESIGN: Cross-sectional study. PATIENT SAMPLE: Resting-state functional magnetic resonance imaging was obtained in 42 migraine individuals and 40 healthy controls (HCs). OUTCOME MEASURES: We calculated the standard deviation (SD) of the BOLD time-series at each voxel and the SD and mean of the dynamic conditional correlation between the brain regions which showed significant group differences in BOLDsv. METHODS: A group comparison was conducted using whole-brain voxel-wise analysis of the standard deviation (SD) of the BOLD time-series which was a measure of the BOLDsv. The brain areas displaying notable group discrepancies in BOLDsv were utilized to outline regions of interest (ROIs). To determine the strength/variability of the dFC, the mean and SD of the dynamic conditional correlation were calculated within these ROIs. Moreover, the postoperative axial pain (PAP) severity of patients was evaluated. RESULTS: Our results revealed that DCM patients with postoperative axial pain (PAP) demonstrated considerably increased BOLDsv in the bilateral thalamus and right insular, but significantly lower BOLDsv in the right S1. By applying dynamic functional connectivity (dFC) analysis, we found that DCM patients with PAP exhibited greater fluctuation of dFC in the thalamo-cortical pathway (specifically, thalamus-S1), when compared to HCs and patients without PAP (nPAP). Lastly, we established that dysfunctional BOLDsv and dFC in the ascending pain pathway were positively associated with the severity of PAP in DCM patients. CONCLUSION: Our results indicate a potential correlation between impaired pain ascending pathway and postoperative axial pain in DCM patients. These findings could potentially spark novel treatment approaches for individuals experiencing preoperative axial pain.

The role of retinal glial cells and related factors in macular edema.

Macular edema (ME) has emerged as a leading cause of visual impairment, representing a critical clinical manifestation and complication associated with many eye diseases. In the occurrence and development of ME, retinal glial cells like Müller cells and microglial cells play vital roles. Moreover, growth factor and cytokines associated with them, such as vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), hypoxia-inducible factor-1α (HIF-1α), angiopoietin-like protein 4 (ANGPTL4), interleukin-6(IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), prostaglandin, etc., also take part in the pathogenesis of ME. Changes in these cytokines can lead to retinal angiogenesis, increased vascular permeability, blood-retinal barrier (BRB) breakdown, and fluid leakage, further causing ME to occur or deteriorate. Research on the role of retinal glial cells and related cytokines in ME will provide new therapeutic directions and effective remedies. This article is a literature review on the role of Müller cells, microglial cells and related factors in ME pathogenesis.

Self-Healing, Laminated, and Low Resistance NH3 Sensor Based on 6,6',6″-(Nitrilotris(benzene-4,1-diyl))tris(5-phenylpyrazine-2,3-dicarbonitrile) Sensing Material Operating at Room Temperature.

With the rapid development of the concept of the Internet of Things (IoT), gas sensors with the function of simulating the human sense of smell became irreplaceable as a key element. Among them, ammonia (NH3) sensors played an important role in respiration tests, environmental monitoring, safety, and other fields. However, the fabrication of the high-performance device with high stability and resistance to mechanical damages was still a challenge. In this work, polyurethane (PU) with excellent self-healing ability was applied as the substrate, and the sensor was designed from new sensitive material design and device structure optimization, through applying the organic molecule with groups which could absorb NH3 and the laminated structure to shorten the electronic transmission path to achieve a low resistance state and favorable sensing properties. Accordingly, a room temperature flexible NH3 sensor based on 6,6',6″-(nitrilotris(benzene-4,1-diyl))tris(5-phenylpyrazine-2,3-dicarbonitrile) (TPA-3DCNPZ) was successfully developed. The device could self-heal by means of a thermal evaporation assisted method. It exhibited a detection limit of 1 ppm at 98% relative humidity (RH), as well as great stability, selectivity, bending flexibility, and self-healing properties. The improved NH3 sensing performance under high RH was further investigated by complex impedance plots (CIPs) and density functional theory (DFT), attributing to the enhanced adsorption of NH3. The TPA-3DCNPZ based NH3 sensors proved to have great potential for application on simulated exhaled breath to determine the severity of kidney diseases and the progress of treatment. This work also provided new ideas for the construction of high-performance room temperature NH3 sensors.

Microfluidic magnetic detection system combined with a DNA framework-mediated immune-sandwich assay for rapid and sensitive detection of tumor-derived exosomes.

Tumor-derived circulating exosomes (TDEs) are being pursued as informative and noninvasive biomarkers. However, quantitatively detecting TDEs is still challenging. Herein, we constructed a DNA tetrahedral-structured probe (TSP)-mediated microfluidic magnetic detection system (µFMS) to provide a rapid and sensitive platform for analyzing TDEs. CD63 aptamer-modified Fe3O4 magnetic nanoparticles (MNPs) were constructed to form magnetic nano-report probes (MNRs). The microfluidic chips were fabricated from glass functionalized with DNA TSP-modified aldehyde groups and a PDMS layer designed with serpentine microchannels. An induction coil-based magnetic detector was used to measure the magnetic signal. The linear dynamic range of the µFMS system for TDE assays was 1.98 × 103-1.98 × 107 particles/mL with a limit of detection of 1.98 × 103 particles/mL in PBS. There was no significant difference in TDE detection between the simulated serum and PBS, which indicated the feasibility of the constructed µFMS system for TDE analysis in complex biological systems. In terms of cost, reaction time and operation procedure, this µFMS has the potential to be developed as a clinical point-of-care testing tool for cancer diagnosis and therapeutics.

Engineering redirected NF-κB/OIP5 expression programs to enhance tumor responses to chemotherapy in bladder cancer.

Nuclear factor kappa-B (NF-κB), a pivotal transcriptional regulator, plays a crucial role in modulating downstream genes implicated in tumor drug resistance. We establish a programmable system within bladder cancer cells to tailor drug responses by employing a synthetic clustered regularly interspaced short palindromic repeats (CRISPR)-based expression strategy that emulates natural transcriptional regulators. Our investigation uncovers the functional significance of Opa-interacting protein 5 (OIP5), upregulated upon NF-κB activation, as a key regulator governing drug-resistance to vincristine (VCR) treatment in bladder cancer. Through engineered guide RNAs (sgRNAs) targeting OIP5 to integrate NF-κB aptamers, we construct a modular scaffold RNA that encodes both the target locus and regulatory functionality. This engineered CRISPR scaffold RNA effectively responds to VCR stimulus by binding with activated NF-κB. Intriguingly, it redirects NF-κB to attenuate OIP5 expression-a reversal of its original role-while concurrently obstructing multiple NF-κB-mediated drug resistance pathways. This dual action thwarts drug resistance development. Further enhancing therapeutic potential, we develop a versatile nanoparticle system capable of co-delivering CRISPR scaffold RNAs and VCR. This synergistic approach demonstrates potent anti-tumor effects in both in vitro and in vivo settings. Our nanoparticle-mediated combination presents a compelling proof-of-concept, showcasing the utility of engineered CRISPR-based synthetic expression programs to reconfigure cellular drug responses and heighten tumor cell susceptibility to chemotherapy.

Feasibility of Symptom Monitoring During the First Year of Endocrine Therapy for Early Breast Cancer Using Patient-Reported Outcomes Collected via Smartphone App.

PURPOSE: Treatment-associated symptoms drive early discontinuation of adjuvant endocrine therapy (ET) for breast cancer. We hypothesized that symptom monitoring with electronic patient-reported outcomes (ePROs) during adjuvant ET will enhance symptom detection, symptom management, and persistence. METHODS: Eligible patients were initiating ET for stage 0-III breast cancer. Participants completed ePRO surveys via smartphone at baseline and 1, 3, 6, and 12 months. Measures included Patient-Reported Outcomes Measurement Information System Anxiety, Depression, Fatigue, and Vaginal Discomfort; plus Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items assessing joint pain, hot flashes, vaginal dryness, concentration problems, and memory problems. Scores surpassing prespecified thresholds triggered alerts, and recommended symptom management pathways were provided to clinicians. The primary objective was to evaluate feasibility, assessed by survey completion rates, with targets of >65% for the baseline survey and ≥1 follow-up survey during the first 6 months. Secondary objectives included 12-month ET discontinuation rate (target: ≤15%), describing symptoms and evaluating pathway implementation. RESULTS: Among 250 participants, 73.2% completed the baseline survey and 69.6% completed ≥1 follow-up survey during the first 6 months. Thirty-one percent of participants had ≥1 symptom alert at baseline and 74% had ≥1 symptom alert during follow-up. The proportions of participants for whom pathway-concordant symptom management was documented at each time point ranged from 12.8% to 36.6%. Twenty-eight participants (11.2%) discontinued ET by 12 months. CONCLUSION: Symptom monitoring with ePROs during adjuvant ET is feasible. Despite infrequent documentation of pathway-concordant symptom management after symptom alerts, ePROs were associated with favorable short-term ET persistence.

Chemical-induced phase transition and global conformational reorganization of chromatin.

Chemicals or drugs can accumulate within biomolecular condensates formed through phase separation in cells. Here, we use super-resolution imaging to search for chemicals that induce phase transition within chromatin at the microscale. This microscopic screening approach reveals that adriamycin (doxorubicin) - a widely used anticancer drug that is known to interact with chromatin - specifically induces visible local condensation and global conformational change of chromatin in cancer and primary cells. Hi-C and ATAC-seq experiments systematically and quantitatively demonstrate that adriamycin-induced chromatin condensation is accompanied by weakened chromatin interaction within topologically associated domains, compartment A/B switching, lower chromatin accessibility, and corresponding transcriptomic changes. Mechanistically, adriamycin complexes with histone H1 and induces phase transition of H1, forming fibrous aggregates in vitro. These results reveal a phase separation-driven mechanism for a chemotherapeutic drug.

Estimating causal effects in observational studies for survival data with a cure fraction using propensity score adjustment.

In observational studies, covariates are often confounding factors for treatment assignment. Such covariates need to be adjusted to estimate the causal treatment effect. For observational studies with survival outcomes, it is usually more challenging to adjust for the confounding covariates for causal effect estimation because of censoring. The challenge becomes even thornier when there exists a nonignorable cure fraction in the population. In this paper, we propose a causal effect estimation approach in observational studies for survival data with a cure fraction. We extend the absolute treatment effects on survival outcomes-including the restricted average causal effect and SPCE-to survival outcomes with cure fractions, and construct the corresponding causal effect estimators based on propensity score stratification. We prove the asymptotic properties of the proposed estimators and conduct simulation studies to evaluate their performances. As an illustration, the method is applied to a stomach cancer study.

Comparison between bioabsorbable magnesium and titanium compression screws for hallux valgus treated with distal metatarsal osteotomies: A meta-analysis.

OBJECTIVES: In this review, we discuss the efficacy and safety of biodegradable magnesium screws compared to titanium screws in the treatment of hallux valgus (HV) in patients undergoing distal metatarsal osteotomy (DMO). MATERIALS AND METHODS: Eligible scientific articles published prior to October 2022 were retrieved from the PubMed, Springer, ScienceDirect, and Cochrane Library databases. The terms used for searching included "hallux valgus", "distal metatarsal osteotomies", and "bioabsorbable magnesium screw" which were limited in the title or abstract through the text. The title and abstract were checked one by one to exclude the non-related studies. For primary identified studies and relevant systematic reviews, the full texts were accessed and browsed to finally include the eligible studies. No restriction was set on publication language and publication status. RESULTS: Two randomized-controlled trials (RCTs) and three non-RCTs that met the inclusion criteria were included. There was no significant difference in the American Orthopaedic Foot and Ankle Society (AOFAS) score, postoperative HV angle (HVA), intermetatarsal angle (IMA), Visual Analog Scale (VAS) score, soft tissue irritation, implant fracture, reoperation, and infection rates between two groups. CONCLUSION: Bioabsorbable magnesium compression screws show comparable clinical or radiological results to titanium compression screws in the treatment of HV in patients undergoing DMO.

Global trends in research of achilles tendon injury/rupture: A bibliometric analysis, 2000-2021.

Background: The Achilles tendon is the strongest and most susceptible tendon in humans. Achilles tendon injuries and ruptures have gradually attracted research attention. However, a bibliometric analysis of global research in this field is lacking. This study involved a bibliometric analysis of the developmental trends and research hotspots in Achilles tendon injuries/ruptures from 2000 to 2021. Methods: Articles published between 2001 and 2021 were retrieved from an extended database of the Science Citation Index using Web of Science. VOSviewer and CiteSpace were used to analyze the relationships between publications, countries, institutions, journals, authors, references, and keywords. Results: This study included 3,505 studies of 73 countries, 3,274 institutions, and 12,298 authors and explored the cooperation between them and the relationships between citations. Over the past 22 years, the number of publications has significantly increased. Foot Ankle International has published the most papers on Achilles tendon injuries/ruptures, and British Journal of Sports Medicine is the most famous journal. Re-rupture, exosomes, acute Achilles tendon rupture, and tendon adhesions gradually become the research focus over the past few years. Conclusion: Achilles tendon injury and rupture are important research topics. A vast number of newly published papers on this topic have demonstrated that clinicians and researchers are interested in their study. Over time, these recent studies will be widely cited; therefore, this bibliometric analysis should be constantly updated.

Reprogramming of human peripheral blood mononuclear cells into induced mesenchymal stromal cells using non-integrating vectors.

Mesenchymal stromal cells (MSCs) have great value in cell therapies. The MSC therapies have many challenges due to its inconsistent potency and limited quantity. Here, we report a strategy to generate induced MSCs (iMSCs) by directly reprogramming human peripheral blood mononuclear cells (PBMCs) with OCT4, SOX9, MYC, KLF4, and BCL-XL using a nonintegrating episomal vector system. While OCT4 was not required to reprogram PBMCs into iMSCs, omission of OCT4 significantly impaired iMSC functionality. The omission of OCT4 resulted in significantly downregulating MSC lineage specific and mesoderm-regulating genes, including SRPX, COL5A1, SOX4, SALL4, TWIST1. When reprogramming PBMCs in the absence of OCT4, 67 genes were significantly hypermethylated with reduced transcriptional expression. These data indicate that transient expression of OCT4 may serve as a universal reprogramming factor by increasing chromatin accessibility and promoting demethylation. Our findings represent an approach to produce functional MSCs, and aid in identifying putative function associated MSC markers.

The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses.

Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1 gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, DACH1 gene deletion within the 13q21.31-q21.33 region occurs in up to 18% of human PCa and was associated with increased AR activity and poor prognosis. In prostate OncoMice, prostate-specific deletion of the Dach1 gene enhanced prostatic intraepithelial neoplasia (PIN), and was associated with increased TGFß activity and DNA damage. Reduced Dach1 increased DNA damage in response to genotoxic stresses. DACH1 was recruited to sites of DNA damage, augmenting recruitment of Ku70/Ku80. Reduced Dach1 expression was associated with increased homology directed repair and resistance to PARP inhibitors and TGFß kinase inhibitors. Reduced Dach1 expression may define a subclass of PCa that warrants specific therapies.

The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses.

Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1 gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, DACH1 gene deletion within the 13q21.31-q21.33 region occurs in up to 18% of human PCa and was associated with increased AR activity and poor prognosis. In prostate OncoMice, prostate-specific deletion of the Dach1 gene enhanced prostatic intraepithelial neoplasia (PIN), and was associated with increased TGFb activity and DNA damage. Reduced Dach1 increased DNA damage in response to genotoxic stresses. DACH1 was recruited to sites of DNA damage, augmenting recruitment of Ku70/Ku80. Reduced Dach1 expression was associated with increased homology directed repair and resistance to PARP inhibitors and TGFb kinase inhibitors. Reduced Dach1 expression may define a subclass of PCa that warrants specific therapies.

Anchoring black phosphorous quantum dots on Bi2WO6 porous hollow spheres: A novel 0D/3D S-scheme photocatalyst for efficient degradation of amoxicillin under visible light.

Reasonable regulation of the micro-morphology of material can significantly enhance the related performance. Herein, bismuth tungstate (Bi2WO6, simplified as BWO) porous hollow spheres with flower-like surface were prepared successfully, and this unique morphology endowed BWO with improved photocatalytic performance by reflecting and absorbing the light multiple times inside the cavity. To inhibit the rapid recombination of photogenerated e--h+ pairs within BWO itself, black phosphorous quantum dots (BPQDs) were anchored onto the nanosheets of BWO sphere closely by a facile self-assembly process, which will not shade the pores of BWO owing to the small size of BPQDs, but the BP nanosheets have the chance to do that. The band gap of BPQDs expanded much after exfoliation due to the quantum confinement effects, which matched the energy band of BWO well to form S-scheme heterojunction, achieving more efficient separation of photogenerated charges. As a result, the BPQDs/BWO exhibited attractive photocatalytic performance in the degradation of amoxicillin (AMX) and other antibiotics. Besides, the operation conditions were optimized, specifically, 94.5 % of AMX (20 mg/L, 200 mL) can be removed in 60 min when 50 mg of 2BPQDs/BWO was used as catalyst with solution pH = 11. Moreover, a possible degradation pathway of AMX was proposed based on the detected intermediates.