Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

Assessment of heavy metal pollution in Laizhou Bay(China)using the ecological risk index and the integrated biomarker response of the goby Acanthogobius ommaturus

We used the Integrated Biological Responses version 2(IBRv2)method to evaluate the biological eff ects of heavy metals in the sediments in Laizhou Bay,China on the benthic goby Acanthogobius ommaturus.In December 2018,gobies and sediments were collected from 15 stations.We measured the activities of defense enzymes and the contents of malondialdehyde(MDA)and metallothionein(MT)in the goby liver as well as the levels of heavy metals in the sediments and goby muscle tissue.Most of the heavy metal concentrations in sediment at each station were below the Class I criteria set by Chinese Standards for Marine Sediment Quality,and the Håkanson ecological risk index suggested low risk for the heavy metals.We found that A.ommaturus could eff ectively accumulate mercury,cadmium,arsenic,and zinc and that the contents of MT and MDA and the activities of glutathione peroxidase and glutathione reductase were suitable biomarkers of heavy metal pollution in this species.The IBRv2 method integrated these four biomarkers and discriminated stations according to heavy metal pollution.Higher IBRv2 values suggested more adverse eff ects in gobies,corroborating more serious heavy metal contamination.The stations with high IBRv2 values and high contents of heavy metals were mainly distributed in the west and northeast parts of the bay.These results show that the IBRv2 approach is a feasible strategy for assessing heavy metal pollution through biological response and biological status and that it can be implemented for environmental monitoring in Laizhou Bay.

Clinical significance of HBME-1,Galectin-3,and CK19 expression and the status of BRAF mutation in papillary thyroid carcinoma

Objective The aim of this study was to explore the clinical significance of the expression of proteins human bone marrow endothelial cell markers(HBME-1), Galectin-3, and cytokeratin19(CK19), as well as the status of v-raf murine sarcoma viral oncogene homolog B1(BRAF) mutation in papillary thyroid carcinoma(PTC). Methods Immunohistochemical staining was performed in 82 specimens each of PTC and papillary benign lesions to detect the expression of HBME-1, Galectin-3, and CK19. Polymerase chain reaction(PCR) and gene sequencing were performed on 60 specimens each of PTC and papillary benign lesions to detect the status of BRAF mutation. Results The positive expression ratios of HBME-1, Galectin-3, and CK19 in PTC were 98.8%, 97.6% and 100% respectively, which were significantly higher than the expressions in papillary benign lesions(P < 0.05). No significant relationship was observed between the expression of these makers and the clinicopathological features of PTC. The sensitivity of co-expression of HBME-1 and CK19 or HBME-1 and Galectin-3 as diagnostic criteria of PTC was 99.9%, with a specificity of 95.4%. BRAF mutation was detected in 40 of 60 PTC(66.7%) specimens. There was a statistical difference in BRAF mutations between PTC and papillary benign lesions(P < 0.05); there were no associations between BRAF mutation and the clinicopathological features of PTC. Conclusion Combined immunohistochemical staining of HBME-1, Galectin-3, and CK19 can further improve the sensitivity and specificity of differential diagnosis of PTC. BRAF mutation is a significant genetic event, which may have diagnostic value for PTC.

3D elastic waveform modeling with an optimized equivalent staggered-grid finite-difference method

Equivalent staggered-grid(ESG) as a new family of schemes has been utilized in seismic modeling,imaging,and inversion.Traditionally,the Taylor series expansion is often applied to calculate finite-difference(FD) coefficients on spatial derivatives,but the simulation results suffer serious numerical dispersion on a large frequency zone.We develop an optimized equivalent staggered-grid(OESG) FD method that can simultaneously suppress temporal and spatial dispersion for solving the second-order system of the 3 D elastic wave equation.On the one hand,we consider the coupling relations between wave speeds and spatial derivatives in the elastic wave equation and give three sets of FD coefficients with respect to the P-wave,S-wave,and converted-wave(C-wave) terms.On the other hand,a novel plane wave solution for the 3 D elastic wave equation is derived from the matrix decomposition method to construct the time-space dispersion relations.FD coefficients of the OESG method can be acquired by solving the new dispersion equations based on the Newton iteration method.Finally,we construct a new objective function to analyze P-wave,S-wave,and C-wave dispersion concerning frequencies.The dispersion analyses show that the presented method produces less modeling errors than the traditional ESG method.The synthetic examples demonstrate the effectiveness and superiority of the presented method.

Scientific challenges of research on natural hazards and disaster risk

As a discipline,the science of natural hazards and disaster risk aims to explain the spatial-temporal pattern,process and mechanism,emergency response and risk mitigation of natural hazards,which requires a multidisci-plinary and interdisciplinary approach.With the support of Natural Science Finance of China(NSFC)and Chinese Academy of Sciences(CAS),in-depth research and systematic analysis on natural hazards and disaster risk were conducted.In this paper,the state of the art in research on natural hazards is summarized from seven aspects:formation process,mechanism and dynamic of natural hazards,disaster risk assessment,forecast,monitoring and early warning,disaster mitigation,emergency treatment and rescue,risk management and post-disaster re-construction.The trends within the natural hazards and disaster risk as a discipline were identified,along with existing shortcomings and significant gaps that need to be addressed.This paper highlighted:1)the scientific challenges including the frontier scientific issues and technological gaps on natural hazards and disaster risk dis-cipline from 2025 to 2035 in China,and 2)the proposal to develop a systemic and holistic natural hazards and disaster risk discipline.

Genome-wide evolution of MAPKs family and their expression in response to bacterial infection in seahorse Hippocampus erectus

Seahorses have evolved many unique biological traits,including a male brood pouch,the absence of caudal and pelvic fins,and the lack of spleen and gut-associated lymphatic tissue.The mitogenactivated protein kinases(MAPKs)are known to be involved in various important biological processes including growth,differentiation,immunity,and stress responses.Therefore,we hypothesized that the adaptive evolution and expression of the MAPK gene family in seahorse may differ from those of other teleost species.We identified positive selection sites in the erk2,erk5,jnk1,and p38αMAPK genes of the lined seahorse Hippocampus erectus and tiger-tailed seahorse Hippocampus comes.A novel expression profile of MAPK cascade genes was found in seahorse larvae during the first day after birth based on the RNA-seq data of H.erectus,which refl ected vital signs of immune response to its parental immune system.The expression patterns of the four positively selected MAPK genes were analyzed following the bacterial challenge of Vibrio fortis,revealing their upregulation pattern in brood pouch and other immune tissues.This study enriched our knowledge of the evolution of the H.erectus MAPK subfamilies,and could help better understanding the functional role of MAPKs in teleosts.

Chromones from an ascomycete,Chaetomium aureus

A novel chromone, named chaetoaurin （1）, along with six known chromone derivatives （2-7）, was isolated from the ethyl acetate extract of a solid-state fermented culture of Chaetomium aureus. Their structures were elucidated by extensive spectral analysis. All of these compounds were reported from C. aureus for the first time.

Process-driven susceptibility assessment of glacial lake outburst debris flow in the Himalayas under climate change

Global warming is causing glaciers to retreat and glacial lakes to expand in the Himalayas,which amplifies the risk of glacial lake outburst debris flows(GLODFs)and poses a significant threat to downstream lives and infrastructures.However,the complex interplay between GLODF occurrences and associated indicators,coupled with the lack of a comprehensive susceptibility indicator system that considers the entire GLODF process,presents a substantial challenge in assessing GLODF susceptibility in the Himalayas.This study proposes a process-driven GLODF susceptibility assessment indicator system responding to climate change that considers the complete process of GLODF formation,incorporating relevant parameters about upstream,themselves,and downstream of glacial lakes.Furthermore,to mitigate subjective factors associated with traditional evaluation methods,we developed three novel hybrid machine-learning models by integrating classic machine-learning algorithms with the whale optimization algorithm(WOA)to delineate the distribution of GLODF susceptibility in the Himalayas.All the hybrid models effectively predicted the GLODFs occurrence,with the WOA-SVC model demonstrating the highest prediction accuracy.Approximately 34%of the catchments exhibit high and very high susceptibility levels,primarily concentrated along the north and south sides of the Himalayan ridge,particularly in the eastern and central Himalayas.Indicators capturing the physical formation process of hazards,such as topographic potential(highest relative importance value of 40%),can precisely identify GLODF.A total of 128 catchments pose potential transboundary threats,with 24 classified as having a very high susceptibility level and 25 as having a high susceptibility level.Notably,the border region between China and Nepal is a prominent hotspot for transboundary threats of GLODF.These findings can provide valuable clues for disaster prevention,mitigation,and cross-border coordination in the Himalayas.

Brain Cognition Mechanism-Inspired Hierarchical Navigation Method for Mobile Robots

Autonomous navigation is a fundamental problem in robotics.Traditional methods generally build point cloud map or dense feature map in perceptual space;due to lack of cognition and memory formation mechanism,traditional methods exist poor robustness and low cognitive ability.As a new navigation technology that draws inspiration from mammal’s navigation,bionic navigation method can map perceptual information into cognitive space,and have strong autonomy and environment adaptability.To improve the robot’s autonomous navigation ability,this paper proposes a cognitive map-based hierarchical navigation method.First,the mammals’navigation-related grid cells and head direction cells are modeled to provide the robots with location cognition.And then a global path planning strategy based on cognitive map is proposed,which can anticipate one preferred global path to the target with high efficiency and short distance.Moreover,a hierarchical motion controlling method is proposed,with which the target navigation can be divided into several sub-target navigation,and the mobile robot can reach to these sub-targets with high confidence level.Finally,some experiments are implemented,the results show that the proposed path planning method can avoid passing through obstacles and obtain one preferred global path to the target with high efficiency,and the time cost does not increase extremely with the increase of experience nodes number.The motion controlling results show that the mobile robot can arrive at the target successfully only depending on its self-motion information,which is an effective attempt and reflects strong bionic properties.

Estimation of Shallow Landslide Susceptibility Incorporating the Impacts of Vegetation on Slope Stability

This study aimed to develop a physical-based approach for predicting the spatial likelihood of shallow landslides at the regional scale in a transition zone with extreme topography.Shallow landslide susceptibility study in an area with diverse vegetation types as well as distinctive geographic factors(such as steep terrain,fractured rocks,and joints)that dominate the occurrence of shallow landslides is challenging.This article presents a novel methodology for comprehensively assessing shallow landslide susceptibility,taking into account both the positive and negative impacts of plants.This includes considering the positive efects of vegetation canopy interception and plant root reinforcement,as well as the negative efects of plant gravity loading and preferential fow of root systems.This approach was applied to simulate the regional-scale shallow landslide susceptibility in the Dadu River Basin,a transition zone with rapidly changing terrain,uplifting from the Sichuan Plain to the Qinghai–Tibet Plateau.The research fndings suggest that:(1)The proposed methodology is efective and capable of assessing shallow landslide susceptibility in the study area;(2)the proposed model performs better than the traditional pseudo-static analysis method(TPSA)model,with 9.93%higher accuracy and 5.59%higher area under the curve;and(3)when the ratio of vegetation weight loads to unstable soil mass weight is high,an increase in vegetation biomass tends to be advantageous for slope stability.The study also mapped the spatial distribution of shallow landslide susceptibility in the study area,which can be used in disaster prevention,mitigation,and risk management.

Risk Assessment of Debris Flows Along the Karakoram Highway (Kashgar‑Khunjerab Section) in the Context of Climate Change

The Karakoram highway(KKH)is renowned for its complex natural environment and geological conditions.The climate changes drastically and directly infuences the frequency and magnitude of debris fows in this region,resulting in signifcant casualties and economic losses.However,the risk assessment of debris fows along the KKH in the context of climate change has been rarely explored.Therefore,in this study we used the debris fow data,historical meteorological data and future climate prediction data to assess the debris fow risk of the study region during the baseline period(2009–2018),2025s(2021–2030),2035s(2031–2040)and 2045s(2041–2050)under the Representative Concentration Pathway 8.5 scenario.The results show that the risk of debris fows increases with climate change,with the highest risk level in the 2025s.Among diferent parts of this highway,the upper reaches of the Ghez River and the second half of Tashkorgan-Khunjerab are the sections with the highest risk.These fndings are helpful for debris fow prevention and can ofer coping strategies for the existing line of the KKH.They also provide some reference for the renovation,improvement,operation,and maintenance of the KKH.

Regulation of T cell immunity by cellular metabolism

T cells are an important adaptive immune response arm that mediates cell-mediated immunity. T cell metabolism plays a central role in T cell activation, proliferation, differentiation, and effector function. Specific metabolic programs are tightly controlled to mediate T cell immune responses, and alterations in T cell metabolism may result in many immunological disorders. In this review, we will summarize the main T cell metabolic pathways and the important factors participating in T cell metabolic programming during T cell homeostasis, differentiation, and function.

Metabolic regulation of T cell development by Sinl-mTORC2 is mediated by pyruvate kinase M2

Glucose metabolism plays a key role in thymocyte development. The mammalian target of rapamycin complex 2 (mT0RC2) is a critical regulator of cell growth and metabolism, but its role in early thymocyte development and metabolism has not been fully studied. We show here that genetic ablation of Sinl, an essential component of mTORC2, in T lineage cells results in severely impaired thymocyte development at the CD4^- CD8^- double negative (DN) stages but not at the CD4^+ CD8^+ double positive (DP) or later stages. Notably, Sinl-deficient DN thymocytes show markedly reduced proliferation and glycolysis.Importantly, we discover that the M2 isoform of pyruvate kinase (PKM2) is a novel and crucial Sinl effector in promoting DN thymocyte development and metabolism. At the molecular level, we show that Sinl-mTORC2 controls PKM2 expression through an AKT-dependent PPAR-y nuclear translocation. Together, our study unravels a novel mTORC2-PPAR-γ-PKM2 pathway in immune-metabolic regulation of early thymocyte development.

An innovative way of etching MoS2： Characterization and mechanistic investigation

We report a systematic study of the etching of MoSs crystals by using XeF2 as a gaseous reactant. By controlling the etching process, monolayer MoS2 with uniform morphology can be obtained. The Raman and photoluminescence spectra of the resulting material were similar to those of exfoliated MoS2. Utilizing this strategy, different patterns such as a Hall bar structure and a hexagonal array can be realized. Furthermore, the etching mechanism was studied by introducing graphene as an etching mask. We believe our technique opens an easy and controllable way of etching MoS2, which can be used to fabricate complex nanostructures, such as nanoribbons, quantum dots, and transistor structures. This etching process using XeF2 can also be extended to other interesting two-dimensional crystals.

Clinical practice guideline for breast-conserving surgery in patients with early-stage breast cancer: Chinese Society of Breast Surgery (CSBrS) practice guidelines 2021

Breast-conserving surgery(BCS)with radiotherapy is the primarily agreed surgical choice for eligible patients with an early diagnosis of breast cancer.In 2019,the panel of Chinese experts assembled by the Chinese Society for Breast Surgery(CSBrS)developed a Chinese experts’consensus on BCS for early-stage breast cancer(Version 2019)with the aim of standardizing BCS in China.Subsequently,the CSBrS conducted a review of published reports and discussions between experts to determine the key clinical questions for the Clinical Practice Guideline for BCS in Patients with Early-Stage Breast Cancer.The group evaluated the relevant evidence using the grading of recommendations assessment,development,and evaluation system,and developed a Clinical Practice Guideline for BCS in Patients with Early-Stage Breast Cancer(Version 2021),with the aim of providing guidance on clinical practice to breast surgeons in China.