Effect of regionalized structures on rock fracture process.

The structure of rocks plays a crucial role in their failure process. However, it is ignored that the interactions between rock internal structure and the effect of its own evolution on the rock fracture process. To investigate the effect between the evolution law of rock regionalized structures and their interaction relationships during failure. We conducted an experiment using visual acoustic imaging monitoring to study rock failure, introducing a new concept of characteristics of rock structure-regionalized structures. The findings reveal three main types of regionalized structures in rocks: skeleton regions, variable regions, and damage regions. These structures combine to form four categories of complex rock structures: block-type support skeletons, point column-type support skeletons, suspension-type weak support skeletons, and no skeletons. During the failure process, we found that these regionalized structures worked together synergistically to control rock failure. Although the evolutionary relationships among the structures show some similarities, the final fracture states vary significantly. Stress and strain distribution patterns clearly demonstrate that variations in the force capacities and roles of the regionalized structures influence the synergistic evolutionary relationships, ultimately impacting the mode of rock failure. This work provides new insights for further research on rock failure mechanisms and can significantly contribute to preventing rock engineering disasters related to regionalized structures.

Reactive oxygen signaling molecule inducible regulation of CRISPR-Cas9 gene editing.

We report development of a controllable gene editing tool that boronated gRNA, simply generated in situ, could regulate binding of gRNA molecules with either Cas9 endonuclease or target genes, thus serving as a modulator that can control CRISPR-Cas9 gene editing. Subsequent treatment with H2O2 facilitates the restoration of gene editing ability of the boronated gRNA to the level of using untreated gRNA. This is one of the few cases using small molecule to regulate CRISPR-Cas9 gene editing, which is a complement to the light approach, displaying great application potential. We develop a controllable gene editing tools based on the CRISPR-Cas9 gene editing system. This tool can be regulated by oxidative small molecule, i.e., H2O2. Compared with the light method, the application scope of our CRISPR-Cas9 systems have been widened with the small-molecule-triggered approaches, preventing the potential damage of cells or organism caused by UV light. In addition, the gain-of-function tools are expanding the gene code expansion for mechanistic studies of target enzymes since it provides a positive route to evaluate the activity of a given enzyme in dynamic and inversible regulation of targeting cellular processes.

Regulation and Site-Specific Covalent Labeling of NSUN2 via Genetic Encoding Expansion.

In living organisms, RNA regulates gene expression, cell migration, differentiation, and cell death. 5-Methylcytosine is a post-transcriptional RNA modification in a wide range of RNA species, including messenger RNAs. The addition of m5C to RNA cytosines is enabled by the NSUN enzyme family, a critical RNA methyltransferase. In this study, natural lysines modified with special groups were synthesized. Through two rounds of positive screening and one round of negative screening, we evaluated and identified the MbPylRS-tRNACUA unnatural lysine substitution system, which specifically recognizes lysine with a defined group. Moreover, non-natural lysine substitution at C271 of NSUN2 active site and the subsequent fluorescent labeling was realized through the click reaction. Then, the function of the NSUN2 mutant and its upregulated CDK1 gene as well as its effect on cell proliferation were evaluated. Efficient labeling and regulation of NSUN2 was achieved, laying the basis for further studies on the function and regulatory mechanism of upregulated genes.

Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial.

IMPORTANCE: Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed. OBJECTIVE: To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021. INTERVENTIONS: Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone. MAIN OUTCOMES AND MEASURES: The primary end point was the 2-year overall survival rate using intention-to-treat analysis. RESULTS: Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02813967.

Stretchable, Stable, and Degradable Silk Fibroin Enabled by Mesoscopic Doping for Finger Motion Triggered Color/Transmittance Adjustment.

As a kind of biocompatible material with long history, silk fibroin is one of the ideal platforms for on-skin and implantable electronic devices, especially for self-powered systems. In this work, to solve the intrinsic brittleness as well as poor chemical stability of pure silk fibroin film, mesoscopic doping of regenerated silk fibroin is introduced to promote the secondary structure transformation, resulting in huge improvement in mechanical flexibility (∼250% stretchable and 1000 bending cycles) and chemical stability (endure 100 °C and 3-11 pH). Based on such doped silk film (SF), a flexible, stretchable and fully bioabsorbable triboelectric nanogenerator (TENG) is developed to harvest biomechanical energy in vitro or in vivo for intelligent wireless communication, for example, such TENG can be attached on the fingers to intelligently control the electrochromic function of rearview mirrors, in which the transmittance can be easily adjusted by changing contact force or area. This robust TENG shows great potential application in intelligent vehicle, smart home and health care systems.

Highly Stretchable, Adhesive, and Self-Healing Silk Fibroin-Dopted Hydrogels for Wearable Sensors.

In recent years, the preparations of flexible electronic devices have attracted great attention. Here, a simple one-pot method of thermal polymerization is introduced to fabricate silk fibroin-dopted hydrogels (SFHs), which are both chemically and physically cross-linked by acrylamide (AM), acrylic acid (AA), and silk fibroin (SF). The addition of SF can effectively enhance the mechanical property of the SFH12% by 59% compared with SFH0% . Taking the advantage of its wide working range of stress (about 0.455-568.9 kPa), the SFH can work as a resistance-type pressure sensor to monitor different human motions. What is more, the excellent adhesion, about 75.17 N m-1 of SFH46% enables it to fit tightly to other objects during the testing, which significantly reduces the loss of small signals due to poor fit. In addition, the SFH demonstrates excellent self-healing property without requiring external excitation and a sensitive temperature response in the range of -10 to 60 °C. The SFH is expected to be applied in the field of electronic skin, soft robots, and other flexible electronic products as well as speech recognition.

Transparent, stretchable and degradable protein electronic skin for biomechanical energy scavenging and wireless sensing.

Self-powered flexible sensors play an increasingly important role in wearable and even implantable electronic devices. Silk protein is an ideal material for flexible sensors because of its terrific biocompatibility and controllable degradation rate. Here, we overcome the problem of mechanical flexibility and poor electrical conductivity of proteins, and develop a highly transparent, biocompatible, full-degradable and flexible triboelectric nanogenerator (Bio-TENG) for energy harvesting and wireless sensing. First, the mechanical flexibility of the silk protein film is greatly enhanced by the mesoscopic functionalization of regenerated silk fibroin (RSF) via adding glycerol and polyurethane (PU). Second, hollow silver nanofibers are constructed on the silk film to form an air-permeable, stretchable, biocompatible and degradable thin layer and utilized as friction electrode. The obtained Bio-TENG demonstrates high transparency (83% by one Ag gird layer), stretchability (Ɛ = 520%) and an instantaneous peak power density of 0.8 W m-2 that can drive wearable electronics. Besides, the Bio-TENG can work as artificial electronic skin for touch/pressure perception, and also for wirelessly controlling Internet of Things as a switch.

A leaf vein-like hierarchical silver grids transparent electrode towards high-performance flexible electrochromic smart windows.

As essential components of numerous flexible and wearable optoelectronic devices, the flexible transparent conducting electrodes (TCEs) with sufficient optical transmittance and electric conductivity become more and more important. In this work, we fabricated a large-area flexible TCE based on leaf vein-like hierarchical metal grids (HMG) comprising of mesoscale "trunk" and microscale "branches". The self-formed branched grids made the conducting paths distributing uniformly while the laser-etching trunk grids enabled to transport the collected electrons across long-distance. The Ag HMG exhibited high optical transmittance (~81%) with low sheet resistance (1.36 Ω sq-1), which could be simply optimized through adjusting the grids' widths, spaces, and the sizes of the TiO2 colloidal crackle patterns. In addition, on the basis of such advanced HMG electrode, flexible electrochromic devices (ECDs) with remarkable cyclic performance were fabricated. The HMG with high transparency, conductivity, and flexibility provides a promising TCE for the next-generation flexible and wearable optoelectronic devices.

MAGEA1 inhibits the expression of BORIS via increased promoter methylation.

Melanoma-associated antigen A1 (MAGEA1) and BORIS (also known as CTCFL) are members of the cancer testis antigen (CTA) family. Their functions and expression-regulation mechanisms are not fully understood. In this study, we reveal new functions and regulatory mechanisms of MAGEA1 and BORIS in breast cancer cells, which we investigated in parental and genetically manipulated breast cancer cells via gene overexpression or siRNA-mediated downregulation. We identified the interaction between MAGEA1 and CTCF, which is required for the binding of MAGEA1 to the BORIS promoter and is critical for the recruitment of DNMT3a. A protein complex containing MAGEA1, CTCF and DNMT3a was formed before or after conjunction with the BORIS promoter. The binding of this complex to the BORIS promoter accounts for the hypermethylation and repression of BORIS expression, which results in cell death in the breast cancer cell lines tested. Multiple approaches were employed, including co-immunoprecipitation, glutathione S-transferase pull-down assay, co-localization and cell death analyses using annexin V-FITC/propidium iodide double-staining and caspase 3 activation assays, chromatin immunoprecipitation and bisulfite sequencing PCR assays for methylation. Our results have implications for the development of strategies in CTA-based immune therapeutics.

SCFSen: A Sensor Node for Regional Soil Carbon Flux Monitoring.

Estimation of regional soil carbon flux is very important for the study of the global carbon cycle. The spatial heterogeneity of soil respiration prevents the actual status of regional soil carbon flux from being revealed by measurements of only one or a few spatial sampling positions, which are usually used by traditional studies for the limitation of measurement instruments, so measuring in many spatial positions is very necessary. However, the existing instruments are expensive and cannot communicate with each other, which prevents them from meeting the requirement of synchronous measurements in multiple positions. Therefore, we designed and implemented an instrument for soil carbon flux measuring based on dynamic chamber method, SCFSen, which can measure soil carbon flux and communicate with each other to construct a sensor network. In its working stage, a SCFSen node measures the concentration of carbon in the chamber with an infrared carbon dioxide sensor for certain times periodically, and then the changing rate of the measurements is calculated, which can be converted to the corresponding value of soil carbon flux in the position during the short period. A wireless sensor network system using SCFSens as soil carbon flux sensing nodes can carry out multi-position measurements synchronously, so as to obtain the spatial heterogeneity of soil respiration. Furthermore, the sustainability of such a wireless sensor network system makes the temporal variability of regional soil carbon flux can also be obtained. So SCFSen makes thorough monitoring and accurate estimation of regional soil carbon flux become more feasible.

[Review on infrared temperature characteristics of acupoints in recent 10 years].

In the paper, the study was reviewed on the infrared temperature characteristics of acupoints in recent 10 years. CNKI, WANFANG, VIP, SciVerse ScienceDirect and Springer databases were retrieved, with"infrared thermal imaging" and "acupoint" as the key words. The retrieving time was from January 1, 2006 to December 31, 2016. Totally, 468 relevant papers were searched and 169 papers of them were read carefully on acupoint infrared temperature. In terms of physiological condition, pathological condition and the stimulation methods such as acupuncture, moxibustion, tuina, embedding therapy and cupping therapy, the general situation was reviewed on the infrared temperature characteristics of acupoints separately. It was found that the study on infrared temperature characteristics of acupoints in physiological condition was limited and the characteristics discovered were not enough to systematically review the physiological and physical properties of acupoints. The study in terms of the pathological condition objectively reflected the effects and rules of diseases. It was showed in the study of acupoint infrared temperature characteristics after stimulation that the changes of infrared thermal imaging tempe-rature at some specific region induced by different therapies and parameters might be used to deduce the potential mechanism and optimal parameters or schemes of intervention method and contributed to the formation and deve-lopment of quantitative diagnosis and treatment. The authors believe that the study on infrared temperature characteristics of acupoint provides the active significance in the exploration on the physiological and physical characteristics of acupoint, the effects and rules of diseases as well as the quantitative diagnosis and treatment.

Haze Removal Using the Difference- Structure-Preservation Prior.

Fog cover is generally present in outdoor scenes, which limits the potential for efficient information extraction from images. In this paper, the goal of the developed algorithm is to obtain an optimal transmission map as well as to remove hazes from a single input image. To solve the problem, we meticulously analyze the optical model and recast the initial transmission map under an additional boundary prior. For better preservation of the results, the difference-structure-preservation dictionary could be learned, such that the local consistency features of the transmission map could be well preserved after coefficient shrinkage. Experimental results show that the method preserves the natural appearance of the image.

The effect of different laser irradiation on cyclophosphamide-induced leucopenia in rats.

Objective. To assess the effect of different lasers on cyclophosphamide- (CTX-) induced leucopenia in rats. Methods. 11 rats were normal control and 55 rats were injected with a dose of 80 mg/kg CTX for the first time and 40 mg/kg on the 6th and the 11th days to establish a leucopenia model. Rats of the irradiation groups received a 5-minute laser irradiation with either single 10.6 µ m or 650 nm laser or alternatively 10.6 µ m-650 nm laser irradiation, besides a sham treatment on acupoint Dazhui (DU 14) and acupoint Zusanli (ST 36) of both sides, 8 times for 16 days. Normal and model control group received no treatment. Results. On day 16 after the first CTX injection, the WBC counts from all the laser irradiation groups were significantly higher than those from the model control and the sham group (P < 0.05), while there were no significant differences compared with the normal control (P > 0.05). The TI of 10.6 µ m-650 nm laser irradiation group was significantly higher than that of the model control group (P < 0.05). Conclusions. The single and combined 10.6 µ m and 650 nm laser irradiation on ST36 and DU14 accelerated the recovery of the WBC count in the rats with leucopenia.

MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a.

MicroRNAs are approximately 21nt single-stranded RNAs and function as regulators of gene expression. Previous studies have shown that microRNAs play crucial roles in tumorigenesis by targeting the mRNAs of oncogenes or tumor suppressors. Here we show that brain-enriched miR-128 is down-regulated in glioma tissues and cell lines when compared to normal brain tissues. Overexpression of miR-128 in glioma cells inhibited cell proliferation. A bioinformatics search revealed a conserved target site within the 3'untranslated region (UTR) of E2F3a, a transcription factor that regulates cell cycle progression. The protein levels of E2F3a in gliomas and normal brain tissues were negatively correlated to the expression levels of miR-128 in these tissues. Overexpression of miR-128 suppressed a luciferase-reporter containing the E2F3a-3'UTR and reduced the level of E2F3a protein in T98G cells. Moreover, knocking down of E2F3a had similar effect as overexpression of miR-128, and overexpression of E2F3a can partly rescue the proliferation inhibition caused by miR-128. Taken together, our study demonstrates that miR-128 can inhibit proliferation of glioma cells through one of its targets, E2F3a.