Assessing base-resolution DNA mechanics on the genome scale.

Intrinsic DNA properties including bending play a crucial role in diverse biological systems. A recent advance in a high-throughput technology called loop-seq makes it possible to determine the bendability of hundred thousand 50-bp DNA duplexes in one experiment. However, it's still challenging to assess base-resolution sequence bendability in large genomes such as human, which requires thousands of such experiments. Here, we introduce 'BendNet'-a deep neural network to predict the intrinsic DNA bending at base-resolution by using loop-seq results in yeast as training data. BendNet can predict the DNA bendability of any given sequence from different species with high accuracy. To explore the utility of BendNet, we applied it to the human genome and observed DNA bendability is associated with chromatin features and disease risk regions involving transcription/enhancer regulation, DNA replication, transcription factor binding and extrachromosomal circular DNA generation. These findings expand our understanding on DNA mechanics and its association with transcription regulation in mammals. Lastly, we built a comprehensive resource of genomic DNA bendability profiles for 307 species by applying BendNet, and provided an online tool to assess the bendability of user-specified DNA sequences (http://www.dnabendnet.com/).

HPV-associated cervicovaginal microbiome and host metabolome characteristics.

BACKGROUND: Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross populations with different habits and regions. Identification of population-specific biomarkers from cervicovaginal microbiota and host metabolome axis may support early detection or surveillance of HPV-induced cervical disease at all sites. Therefore, in the present study, to identify HPV-specific biomarkers, cervicovaginal secretion and serum samples from HPV-infected patients (HPV group, n = 25) and normal controls (normal group, n = 17) in Xichang, China were collected for microbiome (16S rRNA gene sequencing) and metabolome (UHPLC-MS/MS) analysis, respectively. RESULTS: The results showed that key altered metabolites of 9,10-DiHOME, α-linolenic acid, ethylparaben, glycocholic acid, pipecolic acid, and 9,12,13-trihydroxy-10(E),15(Z)-octadecadienoic acid, correlating with Sneathia (Sneathia_amnii), Lactobacillus (Lactobacillus_iners), Atopobium, Mycoplasma, and Gardnerella, may be potential biomarkers of HPV infection. CONCLUSION: The results of current study would help to reveal the association of changes in cervicovaginal microbiota and serum metabolome with HPV infections.

Current understanding of functional peptides encoded by lncRNA in cancer.

Dysregulated gene expression and imbalance of transcriptional regulation are typical features of cancer. RNA always plays a key role in these processes. Human transcripts contain many RNAs without long open reading frames (ORF, > 100 aa) and that are more than 200 bp in length. They are usually regarded as long non-coding RNA (lncRNA) which play an important role in cancer regulation, including chromatin remodeling, transcriptional regulation, translational regulation and as miRNA sponges. With the advancement of ribosome profiling and sequencing technologies, increasing research evidence revealed that some ORFs in lncRNA can also encode peptides and participate in the regulation of multiple organ tumors, which undoubtedly opens a new chapter in the field of lncRNA and oncology research. In this review, we discuss the biological function of lncRNA in tumors, the current methods to evaluate their coding potential and the role of functional small peptides encoded by lncRNA in cancers. Investigating the small peptides encoded by lncRNA and understanding the regulatory mechanisms of these functional peptides may contribute to a deeper understanding of cancer and the development of new targeted anticancer therapies.

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

Is Prophylactic Radiotherapy to the Lymphatic Drainage Area Necessary for Patients With Stage III Ovarian Cancer After Chemotherapy Following Surgery?

BACKGROUND: For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT). Here we assessed the therapeutic efficacy and toxicity of postoperative radiotherapy to the abdominal and pelvic lymphatic drainage area for stage III epithelial ovarian cancer patients, who had all received surgery and chemotherapy (CT). METHODS: We retrospectively collected patients with stage III epithelial ovarian cancer after cytoreductive surgery (CRS) and full-course adjuvant CT. The chemoradiotherapy (CRT) group patients were treated with intensity modulated radiotherapy (IMRT) to the abdominal and pelvic lymphatic drainage area in our hospital between 2010 and 2020. A propensity score matching analysis was conducted to compare the results between the CRT and CT groups. Kaplan-Meier analysis estimated overall survival (OS), disease-free survival (DFS), and local control (LC) rates. The log-rank test determined the significance of prognostic factors. RESULTS: A total of 132 patients with median follow-up of 73.9 months (9.1-137.7 months) were included (44 and 88 for the CRT and RT groups, retrospectively). The baseline characteristics of age, histology, level of CA12-5, surgical staging, residual tumour, courses of adjuvant CT, and courses to reduce CA12-5 to normal were all balanced. The median DFS time, 5-year OS, and local recurrence free survival (LRFS) were 100.0 months vs 25.9 months (P = .020), 69.2% vs 49.9% (P = .002), and 85.9% vs 50.5% (P = .020), respectively. The CRT group mainly presented with acute haematological toxicities, with no statistically significant difference compared with grade III intestinal adverse effects (3/44 vs 6/88, P = .480). CONCLUSION: This report demonstrates that long-term DFS could be achieved in stage III epithelial ovarian cancer patients treated with IMRT preventive radiation to the abdominal and pelvic lymphatic area. Compared with the CT group, DFS and OS were significantly prolonged and adverse effects were acceptable.

Vitamin D deficiency and the risk of diabetic retinopathy in patients with type 2 diabetes in Tibet: a cross-sectional analysis.

BACKGROUND: Diabetic retinopathy (DR) is one of the most common complications of diabetes worldwide. The aim of this study was to assess the prevalence of DR in hospitalized patients with type 2 diabetes (T2DM) in Tibet and to identify risk factors that may influence the occurrence of DR. METHODS: This was a cross-sectional study conducted in a third-class hospital in the Tibet Autonomous Region. The prevalence of DR in hospitalized patients with T2DM was measured. Univariate and multivariate logistic regression, restricted cubic spline (RCS) analysis and receiver-operating characteristic curve analysis were used to investigate the risk factors for DR. RESULTS: The prevalence of DR was 29.3%. The duration of diabetes; concentrations of 25-OH-VitD3, hemoglobin, fasting insulin, alanine aminotransferase, total bilirubin, and creatinine; and HOMA-IR were significantly different between DR patients and non-DR patients (all P < 0.05). Univariate and multivariate logistic regression revealed that a longer duration of diabetes and lower 25-OH-VitD3 levels were associated with increased DR risk. RCS analysis suggested overall positive associations of the duration of diabetes and 25-OH-VitD3 concentrations with DR risk (P nonlinearity < 0.05). The turning points for the duration of diabetes and 25-OH-VitD3 concentrations were 5.1 years and 10.6 ng/mL, respectively. The sensitivity, specificity, and area under the receiver-operating characteristic curve for the combination of the duration of diabetes and 25-OH-VitD3 levels were 79.4%, 69.4% and 0.764, respectively. CONCLUSIONS: Given the high prevalence of DR in hospitalized patients with T2DM in Tibet, vitamin D supplementation seems to be important in the prevention of DR to some degree.

Role of miRNAs in macrophage-mediated kidney injury.

Macrophages, crucial components of the human immune system, can be polarized into M1/M2 phenotypes, each with distinct functions and roles. Macrophage polarization has been reported to be significantly involved in the inflammation and fibrosis observed in kidney injury. MicroRNA (miRNA), a type of short RNA lacking protein-coding function, can inhibit specific mRNA by partially binding to its target mRNA. The intricate association between miRNAs and macrophages has been attracting increasing interest in recent years. This review discusses the role of miRNAs in regulating macrophage-mediated kidney injury. It shows how miRNAs can influence macrophage polarization, thereby altering the biological function of macrophages in the kidney. Furthermore, this review highlights the significance of miRNAs derived from exosomes and extracellular vesicles as a crucial mediator in the crosstalk between macrophages and kidney cells. The potential of miRNAs as treatment applications and biomarkers for macrophage-mediated kidney injury is also discussed.

Connectome-based predictive modeling predicts paranoid ideation in young men with paranoid personality disorder: a resting-state functional magnetic resonance imaging study.

Paranoid personality disorder (PPD), a mental disorder that affects interpersonal relationships and work, is frequently neglected during diagnosis and evaluation at the individual-level. This preliminary study aimed to investigate whether connectome-based predictive modeling (CPM) can predict paranoia scores of young men with PPD using whole-brain resting-state functional connectivity (rs-FC). College students with paranoid tendencies were screened using paranoia scores ≥60 derived from the Minnesota Multiphasic Personality Inventory; 18 participants were ultimately diagnosed with PPD according to the Diagnostic and Statistical Manual of Mental Disorders and subsequently underwent resting-state functional magnetic resonance imaging. Whole-brain rs-FC was constructed, and the ability of this rs-FC to predict paranoia scores was evaluated using CPM. The significance of the models was assessed using permutation tests. The model constructed based on the negative prediction network involving the limbic system-temporal lobe was observed to have significant predictive ability for paranoia scores, whereas the model constructed using the positive and combined prediction network had no significant predictive ability. In conclusion, using CPM, whole-brain rs-FC predicted the paranoia score of patients with PPD. The limbic system-temporal lobe FC pattern is expected to become an important neurological marker for evaluating paranoid ideation.

eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

Association of blood urea nitrogen with all-cause and cardiovascular mortality in hyperlipidemia: NHANES 1999-2018.

OBJECTIVE: Although blood urea nitrogen (BUN) has a crucial impact on many diseases, its effect on outcomes in patients with hyperlipidemia remains unknown. The study aimed to investigate the relationships between BUN levels and all-cause and cardiovascular disease (CVD) mortality in individuals with hyperlipidemia. METHODS: This analysis comprised 28,122 subjects with hyperlipidemia from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The risk of BUN on mortality was evaluated using weighted Cox regression models. Additionally, to illustrate the dose-response association, the restricted cubic spline (RCS) was used. RESULTS: During the observation period, 4276 participant deaths were recorded, of which 1206 were due to CVD. Compared to patients with hyperlipidemia in the third BUN quintile, the hazard ratios (HRs) for all-cause mortality were 1.26 (95% CIs: 1.09, 1.45) and 1.22 (95% CIs: 1.09, 1.37) for patients in the first and fifth quintiles of BUN, respectively. The HRs for CVD mortality among patients in the fifth quintile of BUN were 1.48 (95% CIs: 1.14, 1.93). BUN levels were found to have a U-shaped association with all-cause mortality and a linear association with CVD mortality using restricted triple spline analysis. CONCLUSIONS: This study revealed that both low and high BUN levels in patients with hyperlipidemia are associated with heightened all-cause mortality. Furthermore, elevated BUN levels are also associated with increased CVD mortality. The findings indicate that patients with hyperlipidemia may face an elevated risk of death if they have abnormal BUN levels.

Spontaneous rupture of bladder diverticulum with pseudo renal failure:A case report and literature review.

BACKGROUND: Spontaneous or non-traumatic bladder rupture is rare but can be life-threatening. Bladder rupture caused by a diverticulum is extremely rare, with only a few case reports in medical literature. CASE PRESENTATION: We report the case of a 32-year-old woman admitted to hospital complaints of abdominal pain, oliguria and ascites with no history of trauma. Laboratory tests revealed an elevated serum urea nitrogen(UN) level of 33.5 mmol/l and an elevated creatinine levels of 528 umol/l. X-ray cystography confirmed the rupture of a bladder diverticulum. Subsequent transurethral catheterization led to a prompt increase in urinary output, and serum creatinine level returned to 40 umol/l within 48 h. The patient was successfully treated with laparoscopic diverticulectomy. CONCLUSION: Clinicians should maintain a high level of suspicion for urinary bladder rupture in cases presenting with acute lower abdominal pain, urinary difficulties, and oliguria. When acute renal failure, complicated ascites, and an elevated peritoneal fluid creatinine or potassium level exceeding serum levels are observed, intraperitoneal urine leakage should be suspected without delay. This case emphasizes the importance of early diagnosis and intervention in managing this rare but serious condition.

A comparative study on the effectiveness of online and in-class team-based learning on student performance and perceptions in virtual simulation experiments.

BACKGROUND: The swift transition to online teaching in medical education has presented the challenge of replicating in-class engagement and interaction essential for active learning. Despite online team-based learning (TBL) offering potential solutions through structured cooperative activities, its efficacy in virtual simulation experiment courses remains scantily researched. This study investigates the effectiveness of online TBL for teaching virtual patient experiments in a basic medical laboratory course and contrasts it with traditional offline teaching in terms of student performance and perceptions. METHODS: A comparative analysis involved 179 Year 3 medical students using online TBL, face-to-face TBL (FTF-TBL), and the flipped classroom (FC) approach. The learning outcomes were assessed based on experiment reports, IRAT scores, TRAT scores, and final exam performance. Students' perceptions of both online and in-class TBL methodologies were also surveyed. RESULTS: Both online and in-class TBL groups demonstrated comparable academic outcomes and surpassed the FC group in academic performance. Students displayed a marked preference for the TBL format (whether online or in-class), valuing its enhancement of learning interest and practical knowledge application. Nevertheless, refinements in discussion efficiency, platform convenience, and student-instructor interaction were indicated as potential areas of improvement in the online setting. CONCLUSIONS: Online TBL, along with its in-class counterpart, showed superior academic performance and a more positive learning experience compared to the FC group. These findings underscore the potential of online TBL in adapting to modern pedagogical challenges and enriching medical education through virtual simulation experiments.

The impact of a curriculum-based research training program on medical students' research productivity and future research interests: a longitudinal study.

BACKGROUND: Incorporating scientific research into undergraduate medical education is necessary for the quality of future health care. However, providing rigorous research training to a large number of medical students at one institution remains one of the major challenges. The authors studied the impact of a curriculum-based Research Training Program (RTP) for all undergraduate students at Zhejiang University School of Medicine (ZUSM) on research productivity and future research interests. METHODS: Medical students (n = 2,213) from ZUSM who completed the course of RTP between 2013 and 2020 were studied. The authors measured the academic performance, research publications, and research projects of students across years, and evaluated potential factors that contribute to student research productivity and increased interest in future research. RESULTS: Across the years, there was an increase in the number of student publications, a greater proportion of students with publications, and a greater proportion of projects involving three or more students (P < .01 for all). The academic performance of the course was associated with increased publications (P = .014), whereas overall satisfaction of the course (OR 2.07, 95% CI [1.39, 3.10], P < .001), Skill Composite Score (SCS) (OR 1.70, 95% CI [1.16, 2.50], P = .007), and male gender (OR 1.50, 95% CI [1.06, 2.12], P = .022) were associated with increased future research interests. CONCLUSIONS: The findings suggest that the curriculum-based RTP improved students' research productivity, and that overall program satisfaction and self-assessed performance were associated with increased students' intent to participate in future research.

Chemical profiling and quality evaluation of Liuweizhiji Gegen-Sangshen oral liquid by UPLC-Q-TOF-MS and HPLC-diode array detector fingerprinting.

INTRODUCTION: Liuweizhiji Gegen-Sangshen (LGS) oral liquid is a Chinese patent medicine that is widely used for the prevention and treatment of alcoholic liver disease in clinical practice. However, the chemical complexity of LGS has not yet been investigated. OBJECTIVE: The aim of this study was to rapidly identify chemical constituents of LGS and establish a quality control method based on fingerprint and quantitative analysis. METHODOLOGY: A comprehensive strategy was used by combining qualitative analysis by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and fingerprint analysis by high-performance liquid chromatography with diode array detection (HPLC-DAD). RESULTS: A total of 162 chemical components in LGS, including 91 flavonoids, 31 organic acids, and 20 phenolic compounds, were identified or preliminarily characterized in both positive and negative ion modes based on the UPLC-Q-TOF-MS results. Of these, 37 were confirmed with the reference standards. In fingerprint analysis, 23 peaks were chosen as common peaks and used to evaluate the similarity of different batches of LGS. Subsequently, a rapid quantification method was optimized and validated for the simultaneous determination of multiple chemical markers in LGS. The validated quantitative method was successfully used to analyze different batches of LGS samples. CONCLUSION: The proposed comprehensive strategy combining HPLC-DAD fingerprinting and multi-component quantification demonstrated satisfactory results with high efficiency, accuracy, and reliability. This can be used as a reference for the overall quality consistency evaluation of Chinese patent medicines.

The role of dietary fats on cognition and sarcopenia in the elderly.

BACKGROUND AND OBJECTIVES: To elucidate the role of dietary fats on the relationship between mild cognitive impairment and sarcopenia and help identifying and preventing the decline of cognitive and muscle function in elderly individuals. METHODS AND STUDY DESIGN: The study conducted involving a group of 1812 individuals between the ages of 61 and 92. Body composition and BMR were assessed by bioelectrical impedance analysis. Cognitive function and dietary nutrition were evaluated by neuropsychological assessments and questionnaire of food intake frequency. Lipidomics analysis was performed using UHPLC-Qtrap-MS/MS. RESULTS: MCI and SA are mutual influencing factors, lower intake of MUFA, PUFA and higher intake of fat was associated with cognitive dysfunction and/or SA (p < 0.05). PUFA was important for MCI combined with SA (Compared with Q1, Q4 OR: 0.176, 95%CI: 0.058,0.533). Lipidomics analysis revealed that triacylglycerol (TAG) contain more carbon chains with saturated double bonds may be closely related to cognitive impairment and the progression of SA (p < 0.05). While, DAG with carbon chains of unsaturated double bonds is opposite. CONCLUSIONS: Insufficient intake of unsaturated fatty acids was associated with the development of cognitive decline and the progression of SA. MUFA affecting muscle health, fats and PUFA has a greater impact on MCI combined with SA. Less MUFA intake and increasing saturated double-bonded fatty acid intake might be the key factors on promoting cognitive impairment and SA in the elderly. They have the potential to serve as prospective biomarkers indicating a higher risk of cognitive decline and/or SA in the elderly population.

Penalty Versus Premium: Social Disposition Differentiates Life Satisfaction Among Living-Alone Immigrant and Native-Born Older Adults-Findings From the Canadian Longitudinal Study on Aging (CLSA).

Using data from the Canadian Longitudinal Study on Aging, in this study we provide an alternative explanation for the gap of life satisfaction between living-alone immigrants and Canadian-born older adults. Based on the Big-Five personality traits, we use the latent class analysis to generate two types of social dispositions, social independence and social dependence. With social dispositions taken into account, living alone contributes to life satisfaction in opposite ways for immigrant and Canadian-born older adults, by playing a negative role for the former group and a positive role for the latter. The trend of higher life satisfaction among the living-alone Canadian-born are mainly among the socially independent, whereas for immigrants, socially dependent older adults experience the lowest level of life satisfaction when living alone. Therefore, while socially independent Canadian-born older adults gain a "living-alone premium" in life satisfaction; their socially dependent immigrant counterparts experience a "living-alone penalty" in life satisfaction.

In vitro efficacy of Er:YAG laser-activated irrigation versus passive ultrasonic irrigation and sonic-powered irrigation for treating multispecies biofilms in artificial grooves and dentinal tubules: an SEM and CLSM study.

BACKGROUND: Multispecies biofilms located in the anatomical intricacies of the root canal system remain the greatest challenge in root canal disinfection. The efficacy of Er:YAG laser-activated irrigation techniques for treating multispecies biofilms in these hard-to-reach areas has not been proved. The objective of this laboratory study was to evaluate the effectiveness of two Er:YAG laser-activated irrigation techniques, namely, photon-induced photoacoustic streaming (PIPS) and shock wave-enhanced emission photoacoustic streaming (SWEEPS), in treating multispecies biofilms within apical artificial grooves and dentinal tubules, in comparison with conventional needle irrigation (CNI), passive ultrasonic irrigation (PUI), and sonic-powered irrigation (EDDY). Two types of multispecies root canal biofilm models were established in combination with two assessment methods using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) with the aim to obtain more meaningful results. METHODS: Ninety extracted human single-rooted premolars were chosen for two multispecies biofilm models. Each tooth was longitudinally split into two halves. In the first model, a deep narrow groove was created in the apical segment of the canal wall. After cultivating a mixed bacterial biofilm for 4 weeks, the split halves were reassembled and subjected to five irrigation techniques: CNI, PUI, EDD, PIPS, and SWEEPS. The residual biofilms inside and outside the groove in Model 1 were analyzed using SEM. For Model 2, the specimens were split longitudinally once more to evaluate the percentage of killed bacteria in the dentinal tubules across different canal sections (apical, middle, and coronal thirds) using CLSM. One-way analysis of variance and post hoc multiple comparisons were used to assess the antibiofilm efficacy of the 5 irrigation techniques. RESULTS: Robust biofilm growth was observed in all negative controls after 4 weeks. In Model 1, within each group, significantly fewer bacteria remained outside the groove than inside the groove (P < 0.05). SWEEPS, PIPS and EDDY had significantly greater biofilm removal efficacy than CNI and PUI, both from the outside and inside the groove (P < 0.05). Although SWEEPS was more effective than both PIPS and EDDY at removing biofilms inside the groove (P < 0.05), there were no significant differences among these methods outside the groove (P > 0.05). In Model 2, SWEEPS and EDDY exhibited superior bacterial killing efficacy within the dentinal tubules, followed by PIPS, PUI, and CNI (P < 0.05). CONCLUSION: Er:YAG laser-activated irrigation techniques, along with EDDY, demonstrated significant antibiofilm efficacy in apical artificial grooves and dentinal tubules, areas that are typically challenging to access.

Fused Azulenyl Squaraine Derivatives Improve Phototheranostics in the Second Near-Infrared Window by Concentrating Excited State Energy on Non-Radiative Decay Pathways.

The second near-infrared (NIR-II) theranostics offer new opportunities for precise disease phototheranostic due to the enhanced tissue penetration and higher maximum permissible exposure of NIR-II light. However, traditional regimens lacking effective NIR-II absorption and uncontrollable excited-state energy decay pathways often result in insufficient theranostic outcomes. Herein a phototheranostic nano-agent (PS-1 NPs) based on azulenyl squaraine derivatives with a strong NIR-II absorption band centered at 1092 nm is reported, allowing almost all absorbed excitation energy to dissipate through non-radiative decay pathways, leading to high photothermal conversion efficiency (90.98 %) and strong photoacoustic response. Both in vitro and in vivo photoacoustic/photothermal therapy results demonstrate enhanced deep tissue cancer theranostic performance of PS-1 NPs. Even in the 5 mm deep-seated tumor model, PS-1 NPs demonstrated a satisfactory anti-tumor effect in photoacoustic imaging-guided photothermal therapy. Moreover, for the human extracted tooth root canal infection model, the synergistic outcomes of the photothermal effect of PS-1 NPs and 0.5 % NaClO solution resulted in therapeutic efficacy comparable to the clinical gold standard irrigation agent 5.25 % NaClO, opening up possibilities for the expansion of NIR-II theranostic agents in oral medicine.

Dealloying-Induced Zeolite-like Metal Framework of AB2 Laves Phase Intermetallic Electrocatalysts.

Exploring an efficient and robust electrocatalyst for hydrogen evolution reaction (HER) at high pH and temperature holds the key to the industrial application of alkaline water electrolysis (AWE). Herein, we design an open tunnel structure by dealloying a series of Laves phase intermetallics, i.e., MCo2 and MRu0.25Co1.75 (M = Sc and Zr). The dealloying process can induce a zeolite-like metal framework for ScCo2 and ScRu0.25Co1.75 by stripping Sc metal from the center of a tunnel structure. This structural engineering significantly lowers their overpotentials at a current density of 500 mA/cm2 (η500) ca. 80 mV in 1.0 M KOH. Through a simple process, ScRu0.25Co1.75 can be easily decorated on a carbon cloth substrate and only requires 132 mV to reach 500 mA/cm2. More importantly it can maintain activity over 1000 h in industrial conditions (6.0 M KOH at 333 K), showing its potential for practical industrial applications.

Identification of the deubiquitinase USP28 as a novel molecular therapeutic target of ovarian cancer.

Ubiquitin specific proteinase 28 (USP28) is a member of the deubiquitylating enzymes, which are mainly involved in cell cycle, apoptosis and DNA damage repair. Although USP28 has been found to be upregulated in some tumors, its role in ovarian cancer (OV) remains unclear. Here we show that USP28 was highly expressed in OV samples compared with normal ovarian tissue, and OV patients with higher USP28 levels had a worse prognosis. We found that the abnormal expression of USP28 mRNA in OV was related to the activation of ß-catenin signaling pathway, and USP28 was a transcriptional target gene of the ß-catenin/YAP1/TBX5 complex. In addition, genetic ablation or pharmacological inhibition of USP28 impaired the proliferation ability of OV cells in vitro and in vivo. In conclusion, our findings show that ß-catenin/YAP1/TBX5-mediated aberrant expression of USP28 promotes the malignant phenotype of OV, suggesting that USP28 may be a therapeutic target for OV.