Inhibition of OLR1 reduces SASP of nucleus pulposus cells by targeting autophagy-GATA4 axis.

Targeting cellular senescence and Senescence Associated Secretory Phenotype (SASP) through autophagy has emerged as a promising intervertebral disc (IVD) degeneration (IDD) treatment strategy in recent years. This study aimed to clarify the role and mechanism of autophagy in preventing IVD SASP. Methods involved in vitro experiments with nucleus pulposus (NP) tissues from normal and IDD patients, as well as an in vivo IDD animal model. GATA4's regulatory role in SASP was validated both in vitro and in vivo, while autophagy modulators were employed to assess their impact on GATA4 and SASP. Transcriptomic sequencing identified Oxidized low-density lipoprotein receptor 1 (OLR1) as a key regulator of autophagy and GATA4. A series of experiments manipulated OLR1 expression to investigate associated effects. Results demonstrated significantly increased senescent NP cells (NPCs) and compromised autophagy in IDD patients and animal models, with SASP closely linked to IDD progression. The aged disc milieu impeded autophagic GATA4 degradation, leading to elevated SASP expression in senescent NPCs. Restoring autophagy reversed senescence by degrading GATA4, hence disrupting the SASP cascade. Moreover, OLR1 was identified for its regulation of autophagy and GATA4 in senescent NPCs. Silencing OLR1 enhanced autophagic activity, suppressing GATA4-induced senescence and SASP expression in senescent NPCs. In conclusion, OLR1 was found to control autophagy-GATA4 and SASP, with targeted OLR1 inhibition holding promise in alleviating GATA4-induced senescence and SASP expression while delaying extracellular matrix degradation, offering a novel therapeutic approach for IDD management.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Cascade reaction-based highly sensitive fluorescent sensing systems applicable for dual-pattern fluorescence visualizing of thiophenol flavors in meat products and condiments.

Thiophenols (ArSHs) are widely used as popular flavoring ingredients for making daily dishes. Dissecting the ArSHs contents in common foodstuffs is meaningful in the field of food safety science. Herein, a novel small-molecule sensor 2-(1H-benzo[d]imidazol-2-yl)-3-(2-(2,4-dinitrophenoxy)-4-morpholinophenyl)acrylonitrile (NOSA) has been tailored. The NOSA is able to respond to ArSHs, spontaneously yielding highly green-emissive fluorescent iminocoumarin (I500). This cascade reaction-based strategy is sensitive (limit-of-detection = 2.8 nM), rapid (within 5 min), and selective toward ArSH flavors. Probe NOSA has been applied to the determination of ArSHs in real-life meat products and condiments. Moreover, a far-red fluorescent compound, 2-(7-(diethylamino)-4-(4-(methylthio)styryl)-2H-chromen-2-ylidene)malononitrile (CMMT), has been first combined with NOSA to construct a composite probe NOSA@CMMT for the ratiometric detection of ArSHs (I500/I630). System NOSA@CMMT exhibits a conspicuous fluorescence change from deep-red to light-green. Benefitted from the gorgeous chromatic fluctuation, a smartphone-integrated analysis platform is established for the real-time evaluation of ArSHs level.

SARS-CoV-2: An Updated Review Highlighting Its Evolution and Treatments.

Since the SARS-CoV-2 outbreak, pharmaceutical companies and researchers worldwide have worked hard to develop vaccines and drugs to end the SARS-CoV-2 pandemic. The potential pathogen responsible for Coronavirus Disease 2019 (COVID-19), SARS-CoV-2, belongs to a novel lineage of beta coronaviruses in the subgenus arbovirus. Antiviral drugs, convalescent plasma, monoclonal antibodies, and vaccines are effective treatments for SARS-CoV-2 and are beneficial in preventing infection. Numerous studies have already been conducted using the genome sequence of SARS-CoV-2 in comparison with that of other SARS-like viruses, and numerous treatments/prevention measures are currently undergoing or have already undergone clinical trials. We summarize these studies in depth in the hopes of highlighting some key details that will help us to better understand the viral origin, epidemiology, and treatments of the virus.

Influence of age as a continuous variable on the prognosis of patients with pT1-2N1 breast cancer.

PURPOSE: To assess the influence of age as a continuous variable on the prognosis of pT1-2N1 breast cancer and examine its decision-making value for postmastectomy radiotherapy (PMRT). METHODS: We retrospectively evaluated 5438 patients with pT1-2N1 breast cancer after mastectomy in 11 hospitals. A multivariable Cox proportional hazards regression model with penalized splines was used to examine the relationship between age and oncologic outcomes. RESULTS: The median follow-up was 67.0 months. After adjustments for confounding characteristics, nonsignificant downward trend in locoregional recurrence (LRR) risk was observed with increasing age (P-non-linear association = 0.640; P-linear association = 0.078). A significant non-linear association was found between age and disease-free survival (DFS) and overall survival (OS) (P-non-linear association <0.05; P-linear association >0.05, respectively). The DFS and OS exhibited U-shaped relationships, with the hazard ratios (HRs), reaching a nadir at 50 years old. A decreased risk of LRR with PMRT vs. no PMRT (HR = 0.304, 95% CI: 0.204-0.454) was maintained in all ages. The HR of PMRT vs. no PMRT for DFS and OS gradually increased with age. In patients ≤50 years old, PMRT was independently associated with favorable LRR, DFS, and OS, all P < 0.05). In patients >50 years old, PMRT was independently associated with reduced LRR (P = 0.004), but had no effect on DFS or OS. CONCLUSIONS: Age was an independent prognostic factor for pT1-2N1 breast cancer; PMRT provided survival benefits for patients ≤50 years old, but not for patients >50 years old.

Intraoperative Endplate Injury Following Transforaminal Lumbar Interbody Fusion.

OBJECTIVE: To investigate the incidence, distribution characteristics, risk factors, and clinical outcomes of intraoperative endplate injury (EI) following transforaminal lumbar interbody fusion. METHODS: Patients who underwent single-level transforaminal lumbar interbody fusion from January 2018 to December 2020 were included. The patients were separated into EI and non-EI groups based on computed tomography obtained immediately postoperatively. Demographic, clinical, and radiographic parameters of all patients were analyzed. Clinical outcomes were evaluated by visual analog scale for low back pain and Oswestry Disability Index. RESULTS: This study enrolled 576 patients. Rates of EI were 19.6% (113/576) of patients and 9.9% (114/1152) of endplates. The rate of superior EI was significantly higher than that of inferior EI. The results showed that older age, lower disc height index, and taller cage height were independent risk factors for intraoperative EI. Postoperative drain output, total blood loss, postoperative duration of drainage tube, and postoperative hospital stay in the EI group were significantly greater than in the non-EI group. There were no statistical differences in Oswestry Disability Index and visual analog scale scores at the same time point between the groups. CONCLUSIONS: Rates of EI were 19.6% of patients and 9.9% of endplates. Superior endplates were more susceptible to injury than inferior endplates. Older age, lower disc height index, and taller cage height were independent risk factors for intraoperative EI. Clinical outcomes were not affected by intraoperative EI during early postoperative follow-up.

Unveiling of brain transcriptome of masked palm civet (Paguma larvata) with chronic infection of Toxoplasma gondii.

BACKGROUND: The aim of this study was to gain an understanding of the transcriptomic changes that occur in a wild species when infected with Toxoplasma gondii. The masked palm civet, an artifically domesticated animal, was used as the model of a wild species. Transcriptome analysis was used to study alterations in gene expression in the domesticated masked palm civet after chronic infection with T. gondii. METHODS: Masked palm civets were infected with 105 T. gondii cysts and their brain tissue collected after 4 months of infection. RNA sequencing (RNA-Seq) was used to gain insight into the spectrum of genes that were differentially expressed due to infection. Quantitative reverse-transcription PCR (qRT-PCR) was also used to validate the level of expression of a set of differentially expressed genes (DEGs) obtained by sequencing. RESULTS: DEGs were screened from the sequencing results and analyzed. A total of 2808 DEGs were detected, of which 860 were upregulated and 1948 were downregulated. RNA-Seq results were confirmed by qRT-PCR. DEGs were mainly enriched in cellular process and metabolic process based on gene ontology enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that transcriptional changes in the brain of infected masked palm civets evolved over the course of infection and that DEGs were mainly enriched in the signal transduction, immune system processes, transport and catabolic pathways. Finally, 10 essential driving genes were identified from the immune signaling pathway. CONCLUSIONS: This study revealed novel host genes which may provide target genes for the development of new therapeutics and detection methods for T. gondii infection in wild animals.

Designing of a high-performance fluorescent small molecule enables dual-mode and ultra-sensitive fluorescence visualizing of HSO3- and HClO in dried fruit, beverage, and water samples.

Herein, a novel hemicyanine derivative (E)-3-(1,1-dimethyl-2-(4-(methylthio)styryl)-1H-benzo[e]indol-3-ium-3-yl)propane-1-sulfonate (BIS) has been reasonably designed. Compound BIS is long-wavelength emissive and water-soluble with a large Stokes shift. Intriguingly, probe BIS provides a dual-mode fluorescence response pattern for the sensing of bisulfite (HSO3-) and hypochlorous acid (HClO) with great limit of detections (3.6 and 57.4 nM). First, the 1,4-Michael addition of HSO3- on the conjugated double bond triggers a ratiometric response (I465/I575). Second, the rapid oxidation of HClO on the thioether moiety provides a turn-on response (I575). Evaluation of HSO3- and HClO levels in dried fruit, beverage, and water samples has been carried out with satisfactory results. Moreover, motivated by an impressive chromatic variation (red to blue), smartphone-assisted signal readout system and thin-film sensing platform are facilely constructed for real-time and on-site measurement of HSO3- levels. Furthermore, probe BIS is used for the in vivo imaging of HSO3- in edible fish models.

Securing content-based image retrieval on the cloud using generative models.

Content-based image retrieval (CBIR) with deep neural networks (DNNs) on the cloud has tremendous business and technical advantages to handle large-scale image repositories. However, cloud-based CBIR service raises challenges in image data and DNN model security. Typically, users who wish to request CBIR services on the cloud require their input images remaining confidential. On the other hand, image owners may intentionally (or unintentionally) upload adversarial examples to the cloud servers, which potentially leads to the misbehavior of CBIR services. Generative Adversarial Networks (GANs) can be utilized to defense against such malicious behavior. However, the GANs model, if not well protected, can be easily abused by the cloud to reconstruct the users' original image data. In this paper, we focus on the problem of secure generative model evaluation and secure gradient descent (GD) computation in GANs. We propose two secure generative model evaluation algorithms and two secure minimizer protocols. Furthermore, we propose and implement Sec-Defense-Gan, a secure image reconstruction framework which can keep the image data, the generative model details and corresponding outputs confidential from the cloud. Finally, We carried out a set of benchmarks over two public available image datasets to show the performance and correctness of Sec-Defense-Gan.

GATA4 promotes the senescence of nucleus pulposus cells via NF-κB pathway.

PURPOSE: Cell senescence plays a vital role in intervertebral disc degeneration. The regulatory mechanism of the cellular senescence of nucleus pulposus cells has not been fully elucidated. A recent study identified GATA4 as an emerging regulator of IMR90 cellular senescence. However, whether GATA4 controls senescence in nucleus pulposus cells still needs to be explored. METHODS: Nucleus pulposus cells were exposed to acidified medium mimic the acid environment of intervertebral disc degeneration. RESULTS: We found that GATA4 protein expression was significantly upregulated in older rats and nucleus pulposus cells undergoing stress-induced aging. Moreover, the data indicated that inhibition of GATA4 significantly inhibited the senescence of nucleus pulposus cells cultured under acidic conditions and that over expression of GATA4 promoted a senescence phenotype. The NF-κB pathway has been confirmed in this study to play a role in the regulation of nucleus pulposus cell senescence by GATA4. By using the NF-κB pathway inhibitor, PDTC (100 µmol/L), significantly decreased the IL-6, matrix metallopeptidase (MMP)-2, MMP-3, MMP-9, MMP-13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4, ADAMTS-5 expression level, and increased Aggrecan and typeⅡcollagen expression level in GATA4 transfected nucleus pulposus cells compared with the group in the absence of PDTC. CONCLUSION: This outcome suggested that GATA4 might play a significant role in nucleus pulposus cell senescence through the NF-κB signaling pathway, and GATA4 is a promising target for intervertebral disc degeneration treatment in the future.

Unfolded protein response alleviates acid-induced premature senescence by promoting autophagy in nucleus pulposus cells.

Acid-induced cellular senescence is a critical underlying mechanism of intervertebral disc (IVD) degeneration (IDD). Acid stimulation activates a variety of biological changes including autophagy, endoplasmic reticulum stress, and related unfolded protein response (UPR), which are important regulators of cellular senescence. However, the precise mechanism of acid-mediated UPR and autophagy in nucleus pulposus cell (NPC) senescence has not been fully elucidated. In this study, we used acid to mimic the acidic microenvironment of IVD, and rat NPCs were cultured with or without autophagy or UPR signaling small-interfering RNAs. The related proteins and genes were assessed by immunofluorescence staining assay, Western blot analyses, and quantitative real-time polymerase chain reaction to monitor the activation of these signals and classify the molecular mechanisms underlying the correlation between autophagy and UPR pathway. Cell cycle analyses, senescence-associated ß-galactosidase staining, gene expression, and immunoblotting analyses were performed to observe NPC senescence. Results showed that acid stimulation not only induced NPC senescence, but also initiated UPR and autophagy. Silencing the binding immunoglobulin protein signaling of UPR or autophagy signaling promoted rat NPC senescence. Knock-down of the UPR also blocked NPC autophagy. Taken together, UPR inhibits NPC senescence under acidic condition by activating autophagy. Hence, UPR-dependent autophagy could be an effective biologic target for the treatment of IDD in the future.

Effect of postmastectomy radiotherapy on pT1-2N1 breast cancer patients with different molecular subtypes.

OBJECTIVE: To clarify the effect of postmastectomy radiotherapy (PMRT) on pT1-2N1 breast cancer patients with different molecular subtypes. METHODS: We retrospectively analyzed the data of 5442 patients with pT1-2N1 breast cancer treated using modified radical mastectomy in 11 hospitals in China. Univariate, multivariate, and propensity score matching (PSM) analyses were used to evaluate the effect of PMRT on locoregional recurrence (LRR). RESULTS: With a median follow-up duration of 63.8 months, the 5-year LRR rates were 4.0% and 7.7% among patients treated with and without PMRT, respectively (p < 0.001). PMRT was independently associated with reduced LRR after adjustments for confounders (p < 0.001). After grouping the patients according to the molecular subtype of cancer and conducting PSM, we found that the 5-year LRR rates among patients treated with and without PMRT (in that order) were as follows: luminal HER2-negative cancer, 1.9% and 6.5% (p < 0.001); luminal HER2-positive cancer, 3.8% and 13.7% (p = 0.041); HER2-overexpressing cancer, 10.2% and 15.5% (p = 0.236); and triple-negative cancer, 4.6% and 15.9% (p = 0.002). Among patients with HER2-overexpressing and triple-negative cancers, the LRR hazard rate displayed a dominant early peak, and was extremely low after 5 years. However, patients with luminal cancer continued to have a long-lasting high annual LRR hazard rate during follow-up. CONCLUSION: PMRT significantly reduced the LRR risk in patients with pT1-2N1 luminal and triple-negative breast cancers, but had no effect on the LRR risk in patients with HER2-overexpressing cancer. Patients with different molecular subtypes displayed different annual LRR patterns, and the late recurrence of the luminal subtype suggests the necessity of long-term follow-up to evaluate the efficacy of PMRT.

ZIF-8@GMP-Tb nanocomplex for ratiometric fluorescent detection of alkaline phosphatase activity.

Luminescent metal-organic frameworks (LMOFs) and their functional materials with unique characteristics can provide the basis for the construction of new analytical techniques, which can meet the continuous demand for various fields. In this work, guanosine monophosphate (GMP), terbium ion (Tb3+) and zeolitic imidazolate framework-8 (ZIF-8) are self-assembled to form a ZIF-8@GMP-Tb nanocomplex, which can be utilized as a ratiometric fluorescent probe to monitor alkaline phosphatase (ALP) activity. Specifically, with adding ALP, the fluorescence intensity at 547 nm (one of the characteristic emission peaks of Tb3+) obviously decreased. Meanwhile, the conjugated structure of GMP increased the fluorescence of ZIF-8 (located at 330 nm). The possible mechanism was proposed through the characterization of the materials. Based on the variation of the emission peaks at 330 and 547 nm, the ratiometric fluorescent sensor of ALP has a linear range of 0.25-20 U/L. Moreover, applying this sensing system to the detection of ALP in the human serum sample and ALP inhibitor investigation possesses satisfactory results. This work provides a new perspective for the utilization of ZIF-8 and lanthanide ions in manufacturing simple and sensitive sensors.

[Targeted one channel percutaneous transforaminal endoscopic discectomy for the treatment of adjacent segment degeneration after spinal fusion surgery in young patients].

OBJECTIVE: To compare clinical efficacy between targeted one-channel percutaneous transforaminal endoscopic discectomy (TO-PTED) and transforaminal lumbar interbody fusion (TLIF) in treatment of adjacent segment degeneration (ASD) after spinal fusion surgery in young patients. METHODS: The clinical data of 64 patients with adjacent segment degeneration after spinal fusion fusion surgery from September 2017 to February 2019 were retrospectively analyzed. Among them, 30 patients were treated with TO-PTED (TO-PTED group), there were 19 males and 11 females, aged from 23 to 34 years, with a mean of(31.20±1.67) years;the course of disease was from 10 to 39 months, with a mean of (26.30±0.41) months. And other 34 patients were treated with TILF(TILF group), there were 21 males and 13 females, aged from 22 to 34 years, with a mean of (31.10±1.74) years;the course of disease was from 11 to 40 months, with a mean of (27.10±0.32) months. The operation time, intraoperative blood loss, hospitalization time, X-ray fluoroscopy times were compared between two groups. Visual analogue scale(VAS) and Japanese Orthopaedic Association(JOA) scores were used to evaluate the clinical efficacy between two groups before operation, 1 month after operation and at the final follow-up. RESULTS: Operation time, intraoperative blood loss, hospitalization time, X-ray fluoroscopy times were (76.30±5.08) min, (38.80±4.21) ml, (3.90±1.13) d, (8.80±2.53) times in TO-PTED group, and (118.50±11.06) min, (162.71±19.31)ml, (7.30±1.42)d, (4.10±0.82) times in TLIF group, respectively, the difference between the two groups was statistically significant. All patients were followed up from 12 to 24 months, with a mean of (18.00±5.63) months. VAS and JOA scores at 1 month after surgery and at final follow-up were obviously improved, and TO-PTED group was superior than TLIF group. CONCLUSION: Both TO-PTED and TLIF can achieve good results in the treatment of adjacent segment degeneration after spinal fusion surgery in young patients. TO-PTED has advantages in reducing operation time, intraoperative blood loss and postoperative recovery time, but it will increase the number of patients receiving intraoperative radiation.

Selenium-induced NiSe2@CuSe2 hierarchical heterostructure for efficient oxygen evolution reaction.

Electrochemical water splitting is widely studied in the hope of solving environmental deterioration and energy shortage. The design of inexpensive metal catalysts exhibiting desired catalytic performance and durable stability for efficient oxygen evolution is the pursuit of sustainable and clean energy fields. Herein, a three-dimensional (3D) flower-like NiSe2 primary structure, modified with highly dispersed CuSe2 nanoclusters as the secondary structure, is obtained by regulating the growth trend of the nanosheets. Benefiting from the metallicity of selenides and the formation of a heterogeneous interface, NiSe2@CuSe2/NF shows comparable performance toward the oxygen evolution reaction (OER) in an alkaline environment. Upon regulating the synthesis conditions, the catalyst exhibits its optimal performance with ultralow overpotential for the OER when the Ni/Cu molar ratio is 1 : 0.2 and the hydrothermal temperature and hydrothermal time are 200 °C and 6 h, respectively. It provides a current density of 10 mA cm-2 when a potential of 201 mV is applied without iR compensation. In this work, the hierarchical heterostructures of NiSe2 and CuSe2 are synthesized, which exhibit high electrocatalytic activity towards the oxygen evolution reaction and provides a new possibility for the extensive application of copper-based compounds in advanced energy fields.

The Efficacy and Safety of Carbon Ion Radiotherapy for Meningiomas: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this systematic review and meta-analysis is to evaluate the efficacy and safety of carbon ion radiotherapy (CI-RT) in improving meningioma by comparing photon and protons radiotherapy. METHODS: A comprehensive search for relevant studies published until March 17, 2021, was conducted in PubMed, the Cochrane Library, Chinese Biomedical Literature Database and EMBASE. Statistical analyses were performed with R 4.0.3. RESULTS: We identified 396 studies, of which 18 studies involving 985 participants were included. Except for one low quality study, the quality of the included studies was found to be either moderate or high quality. The analyses conducted according random effects model indicated that the 1-year overall survival rate (OS) of benign and non-benign meningiomas after the CI-RT treatment was 99% (95%CL=.91-1.00, I 2 = 0%). The overall average 5-year OS for meningiomas was 72% (95%CL=0.52-0.86, I 2 = 35%), not as effective as proton radiotherapy (PR-RT) 85% (95%CL=.72-.93, I 2 = 73, Q=4.17, df=2, p=.12). Additionally, 5-year OS of atypical meningiomas (81%) was found to be significantly higher than anaplastic meningiomas (52%). The 10-year OS after CI-RT of patients with mixed grade meningioma was 91% (95%CL=.75-.97, I 2 = 73%). The 15-year OS after CI-RT 87% (95%CL=.11-1.00) or PR-RT 87% (95%CL=.23-.99, I 2 = 79%) were the same (Q=0, df=1, p=.99). After undergoing CI-RT for 3 and 5 years, the LC for benign meningioma was 100% and 88%, respectively, while the 2-year LC of non-benign meningiomas (atypical/anaplastic) was 33%. Headache, sensory impairment, cognitive impairment, and hearing impairment were found to be the most common adverse reactions, with individual incidences of 19.4%, 23.7%, 9.1%, and 9.1%, respectively. CONCLUSION: CI-RT is a rapidly developing technique that has been proven to be an effective treatment against meningioma. The efficacy and safety of CI-RT for meningiomas were similar to those of PR-RT, better than photon radiotherapy (PH-RT). However, there is a need for more prospective trials in the future that can help provide more supportive evidence.

Crystal Violet-Sensitized Direct Z-Scheme Heterojunction Coupled with a G-Wire Superstructure for Photoelectrochemical Sensing of Uracil-DNA Glycosylase.

Dye sensitization achieving photoelectrochemical (PEC) signal amplification for ultrasensitive bioanalysis has undergone a major breakthrough. In this proposal, an innovative PEC sensing platform is developed by combining Z-scheme WO3@SnS2 photoactive materials and a G-wire superstructure as well as a dye sensitization enhancement strategy. The newly synthesized WO3@SnS2 heterojunction with outstanding PEC performance is employed as a photoelectrode matrix. Due to the formation of the Z-scheme heterojunction between WO3 and SnS2, the migration dynamics of the photogenerated carrier is evidently augmented. To improve sensitivity, the target excision-driven dual-cycle signal amplification strategy is introduced to output exponential c-myc fragments. Crystal violet is then conjugated into the G-quadruplex to amplify the PEC signal, where crystal violet generates excited electrons by capturing visible light and rapidly injects electrons into the conduction band of SnS2, suppressing the recombination of the photo-induced carrier. Moreover, the G-wire superstructure acts as a universal amplification pathway, ensuring adequate crystal violet loads. Specifically, the biosensor for uracil-DNA glycosylase quantification displays a wide detection range (0.0005-1.0 U/mL) and a lower detection limit (0.00025 U/mL). Furthermore, the Z-scheme electron migration mechanism and the crystal violet sensitization effect are discussed in detail. The construction of the PEC sensor provides a new consideration for signal amplification and material design.

One-pot synthesis of Mn-Fe bimetallic oxide heterostructures as bifunctional electrodes for efficient overall water splitting.

The design of Earth-abundant and cost-effective electrocatalysts for highly active and stable electrochemical water splitting in practical production is the primary demand. Herein, bimetallic oxides anchored to three-dimensional (3D) porous conductive nickel foam (NF) are constructed using a simple in situ hydrothermal method for efficient overall water splitting. The vertically aligned Mn3O4/Fe2O3 heterojunction nanosheets have synergy between hierarchical metal oxides and heterogeneous interface, and show excellent performance toward the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in an alkaline environment. By adjusting the molar ratio of Fe : Mn, the morphology, composition and electronic structure of MnFeO-NF-x composites (x represents the ratio of Fe : Mn) can be adjusted to exhibit diverse catalytic activities. In particular, MnFeO-NF-0.4 (0.4 indicates the Fe : Mn ratio of 0.4 : 1) and MnFeO-NF-0.8 display outstanding performance with ultralow overpotentials of 157 mV for the OER and 64 mV for the HER to achieve a current density of 10 mA cm-2, respectively. Furthermore, MnFeO-NF-0.4 and MnFeO-NF-0.8 are assembled into a water splitting electrolyzer, which can reach a current density of 10 mA cm-2 with a low voltage of 1.59 V. Interestingly, Mn-M (M = Co, Ni, and Mo) products can be obtained easily by using different metal salts, indicating the universality of the current one-pot hydrothermal method.

Nomogram predicting survival as a selection criterion for postmastectomy radiotherapy in patients with T1 to T2 breast cancer with 1 to 3 positive lymph nodes.

BACKGROUND: The role of postmastectomy radiotherapy (PMRT) in women with pT1-T2N1 breast cancer is controversial. The authors developed a nomogram that was predictive for overall survival (OS) and identified patients who derived no benefit from PMRT. METHODS: The authors retrospectively evaluated 4869 patients with pT1-T2N1 breast cancer who were treated with mastectomy between 2000 and 2014 in 11 Chinese hospitals. Rates of locoregional recurrence and distant metastasis were calculated using competing risk analysis, and disease-free survival and OS rates were calculated using the Kaplan-Meier method. Based on the risk factors identified from Cox regression analysis in 3298 unirradiated patients, a nomogram predicting OS was developed. The benefit of PMRT was evaluated in different risk groups stratified by the nomogram model. RESULTS: After a median follow-up of 65.9 months, the 5-year OS, disease-free survival, locoregional recurrence, and distant metastasis rates were 93.3%, 84.3%, 5.2%, and 8.3%, respectively. A total of 1571 patients (32.3%) underwent PMRT. On multivariable analyses, PMRT was found to increase OS significantly (hazard ratio, 0.61; P = .002). An OS prediction nomogram evaluated the effect of age; tumor location; tumor size; positive lymph node ratio; estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status; and treatment with trastuzumab. Based on nomogram scores, the entire patient cohort was classified into 3 risk groups. PMRT significantly improved the OS of patients in the intermediate-risk (P < .001) and high-risk groups (P = .004), but not in the low-risk group (P = .728). CONCLUSIONS: The authors developed a nomogram that is predictive of OS among women with pT1-T2N1 breast cancer after mastectomy. This nomogram may help to select a subgroup of patients with a good prognosis who will not benefit from PMRT.