Research Progress in Targeted Therapy for Esophageal Cancer

Esophageal cancer (EC) is a prevalent malignant tumor that affects the digestive system and is often linked to a poor prognosis. The absence of effective early screening methods results in the diagnosis of esophageal cancer (EC) patients at advanced or metastatic stages. While historically considered incurable, ongoing advancements in medical research have led to the integration of various treatment modalities as primary approaches for managing advanced endometrial cancer. These modalities include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Notably, the introduction of targeted therapy and immunotherapy has significantly enhanced the survival rates of individuals with EC. Immunotherapy has appeared as the predominant treatment for advanced esophageal cancer, while targeted therapy faces certain obstacles. Consequently, this review primarily focuses on the advancements in targeted therapy for esophageal cancer (EC), evaluating the effectiveness and safety of relevant medications, and aiming to provide guidance for the comprehensive management of EC based on current research findings.

Research Progress on the Bone Metastasis Mechanism of Prostate Cancer and Bone-Targeted Drugs

Prostate cancer is a common male malignant tumor,and bone metastasis is one of the common complications in the late stage of prostate cancer.The mechanism of prostate cancer bone metastasis is a complex process involving multiple factors and steps.In recent years,with in-depth research on the mechanism of prostate cancer bone metastasis and the development of new drugs,important progress has been made in the treatment of prostate cancer bone metastasis.Based on this,this article introduces the mechanism of prostate cancer bone metastasis and the research progress of several bone-targeted drugs to provide reference and inspiration for future research.

Mitochondrial targeting sequence of magnetoreceptor MagR:More than just targeting

Iron-sulfur clusters(ISC)are essential cofactors for proteins involved in various biological processes,such as electron transport,biosynthetic reactions,DNA repair,and gene expression regulation.ISC assembly protein IscA1(or MagR)is found within the mitochondria of most eukaryotes.Magnetoreceptor(MagR)is a highly conserved A-type iron and iron-sulfur cluster-binding protein,characterized by two distinct types of iron-sulfur clusters,[2Fe-2S]and[3Fe-4S],each conferring unique magnetic properties.MagR forms a rod-like polymer structure in complex with photoreceptive cryptochrome(Cry)and serves as a putative magnetoreceptor for retrieving geomagnetic information in animal navigation.Although the N-terminal sequences of MagR vary among species,their specific function remains unknown.In the present study,we found that the N-terminal sequences of pigeon MagR,previously thought to serve as a mitochondrial targeting signal(MTS),were not cleaved following mitochondrial entry but instead modulated the efficiency with which iron-sulfur clusters and irons are bound.Moreover,the N-terminal region of MagR was required for the formation of a stable MagR/Cry complex.Thus,the N-terminal sequences in pigeon MagR fulfil more important functional roles than just mitochondrial targeting.These results further extend our understanding of the function of MagR and provide new insights into the origin of magnetoreception from an evolutionary perspective.

High-speed penetration of ogive-nose projectiles into thick concrete targets:Tests and a projectile nose evolution model

The majority of the projectiles used in the hypersonic penetration study are solid flat-nosed cylindrical projectiles with a diameter of less than 20 mm.This study aims to fill the gap in the experimental and analytical study of the evolution of the nose shape of larger hollow projectiles under hypersonic penetration.In the hypersonic penetration test,eight ogive-nose AerMet100 steel projectiles with a diameter of 40 mm were launched to hit concrete targets with impact velocities that ranged from 1351 to 1877 m/s.Severe erosion of the projectiles was observed during high-speed penetration of heterogeneous targets,and apparent localized mushrooming occurred in the front nose of recovered projectiles.By examining the damage to projectiles,a linear relationship was found between the relative length reduction rate and the initial kinetic energy of projectiles in different penetration tests.Furthermore,microscopic analysis revealed the forming mechanism of the localized mushrooming phenomenon for eroding penetration,i.e.,material spall erosion abrasion mechanism,material flow and redistribution abrasion mechanism and localized radial upsetting deformation mechanism.Finally,a model of highspeed penetration that included erosion was established on the basis of a model of the evolution of the projectile nose that considers radial upsetting;the model was validated by test data from the literature and the present study.Depending upon the impact velocity,v0,the projectile nose may behave as undistorted,radially distorted or hemispherical.Due to the effects of abrasion of the projectile and enhancement of radial upsetting on the duration and amplitude of the secondary rising segment in the pulse shape of projectile deceleration,the predicted DOP had an upper limit.

Precision targeting in hepatocellular carcinoma:Exploring ligandreceptor mediated nanotherapy

Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages,but it is often ineffective and suffers from problems such as multidrug resistance,rapid drug clearance,nonspecific targeting,high side effects,and low drug accumulation in tumor cells.In response to these limitations,recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC.This review focuses on recent advances in nanoparticle-based targeted drug delivery systems,with special attention to various receptors overexpressed on HCC cells.These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC.We comprehensively summarize the current understanding of these receptors,their role in nanoparticle targeting,and the impact of such targeted therapies on HCC.By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies,more effective and precise treatment of HCC can be achieved.

Real-time Rescue Target Detection Based on UAV Imagery for Flood Emergency Response

Timely acquisition of rescue target information is critical for emergency response after a flood disaster.Unmanned Aerial Vehicles(UAVs)equipped with remote sensing capabilities offer distinct advantages,including high-resolution imagery and exceptional mobility,making them well suited for monitoring flood extent and identifying rescue targets during floods.However,there are some challenges in interpreting rescue information in real time from flood images captured by UAVs,such as the complexity of the scenarios of UAV images,the lack of flood rescue target detection datasets and the limited real-time processing capabilities of the airborne on-board platform.Thus,we propose a real-time rescue target detection method for UAVs that is capable of efficiently delineating flood extent and identifying rescue targets(i.e.,pedestrians and vehicles trapped by floods).The proposed method achieves real-time rescue information extraction for UAV platforms by lightweight processing and fusion of flood extent extraction model and target detection model.The flood inundation range is extracted by the proposed method in real time and detects targets such as people and vehicles to be rescued based on this layer.Our experimental results demonstrate that the Intersection over Union(IoU)for flood water extraction reaches an impressive 80%,and the IoU for real-time flood water extraction stands at a commendable 76.4%.The information on flood stricken targets extracted by this method in real time can be used for flood emergency rescue.

Advantages of nanocarriers for basic research in the field of traumatic brain injury

A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.

Mitophagy in intracerebral hemorrhage:a new target for therapeutic intervention

Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.

Humanβ-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long noncoding RNA TCONS_00014506

BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.

Progress in the research of cuproptosis and possible targets for cancer therapy

Developing novel cancer therapies that exploit programmed cell death pathways holds promise for advancing cancer treatment.According to a recently published study in Science,copper death(cuproptosis)occurs when intracellular copper is overloaded,triggering aggregation of lipidated mitochondrial proteins and Fe–S cluster proteins.This intriguing phenomenon is triggered by the instability of copper ions.Understanding the molecular mechanisms behind cuproptosis and its associated genes,as identified by Tsvetkov,including ferredoxin 1,lipoic acid synthase,lipoyltransferase 1,dihydrolipid amide dehydrogenase,dihydrolipoamide transacetylase,pyruvate dehydrogenaseα1,pyruvate dehydrogenaseβ,metallothionein,glutaminase,and cyclin-dependent kinase inhibitor 2A,may open new avenues for cancer therapy.Here,we provide a new understanding of the role of copper death and related genes in cancer.

Research progress on natural products against hepatocellular carcinoma

Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable prognosis.In the relentless pursuit of effective treatment modalities,natural products have emerged as a promising and relatively non-toxic alternative,garnering significant interest.The integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of HCC.This review offers a comprehensive overview of the causal factors underlying HCC,and the diverse treatment options available,and highlights the advancements made by natural products in anti-HCC research.Particularly,we provide an outline of the various types of natural products,their corresponding nomenclature,target molecules,and mechanisms of action that exhibit anti-HCC activities.Natural products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer,potentially offering patients improved survival rates and an enhanced quality of life.

Research progress on dynamic monitoring of ctDNA and drug resistance related concomitant mutations in non-small cell lung cancer

Owing to significantly prolonged survival,targeted therapy has become standardized recommendation for advanced non-small cell lung cancer patients with mutated driver genes.However,the genetic status of lung cancer patients is dynamic.By dynamically monitoring the evolution of genes status,differential genes and concomitant genes related to progressive disease could be confirmed early,so as to achieve a more accurate and comprehensive insight of the whole process management of targeted therapy for lung cancer patients.Under the guidance of accurate genetic testing results,it is helpful to provide patients with more effective,long-term,and stable individualized targeted therapy.

Can ChatGPT evaluate research quality?

Purpose:Assess whether ChatGPT 4.0 is accurate enough to perform research evaluations on journal articles to automate this time-consuming task.Design/methodology/approach:Test the extent to which ChatGPT-4 can assess the quality of journal articles using a case study of the published scoring guidelines of the UK Research Excellence Framework(REF)2021 to create a research evaluation ChatGPT.This was applied to 51 of my own articles and compared against my own quality judgements.Findings:ChatGPT-4 can produce plausible document summaries and quality evaluation rationales that match the REF criteria.Its overall scores have weak correlations with my self-evaluation scores of the same documents(averaging r=0.281 over 15 iterations,with 8 being statistically significantly different from 0).In contrast,the average scores from the 15 iterations produced a statistically significant positive correlation of 0.509.Thus,averaging scores from multiple ChatGPT-4 rounds seems more effective than individual scores.The positive correlation may be due to ChatGPT being able to extract the author’s significance,rigour,and originality claims from inside each paper.If my weakest articles are removed,then the correlation with average scores(r=0.200)falls below statistical significance,suggesting that ChatGPT struggles to make fine-grained evaluations.Research limitations:The data is self-evaluations of a convenience sample of articles from one academic in one field.Practical implications:Overall,ChatGPT does not yet seem to be accurate enough to be trusted for any formal or informal research quality evaluation tasks.Research evaluators,including journal editors,should therefore take steps to control its use.Originality/value:This is the first published attempt at post-publication expert review accuracy testing for ChatGPT.

Target acquisition performance in the presence of JPEG image compression

This paper presents an investigation on the effect of JPEG compression on the similarity between the target image and the background,where the similarity is further used to determine the degree of clutter in the image.Four new clutter metrics based on image quality assessment are introduced,among which the Haar wavelet-based perceptual similarity index,known as HaarPSI,provides the best target acquisition prediction results.It is shown that the similarity between the target and the background at the boundary between visually lossless and visually lossy compression does not change significantly compared to the case when an uncompressed image is used.In future work,through subjective tests,it is necessary to check whether this presence of compression at the threshold of just noticeable differences will affect the human target acquisition performance.Similarity values are compared with the results of subjective tests of the well-known target Search_2 database,where the degree of agreement between objective and subjective scores,measured through linear correlation,reached a value of 90%.

Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development.The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

Research funding and citations in papers of Nobel Laureates in Physics, Chemistry and Medicine, 2019-2020

Purpose:The goal of this study is a comparative analysis of the relation between funding(a main driver for scientific research)and citations in papers of Nobel Laureates in physics,chemistry and medicine over 2019-2020 and the same relation in these research fields as a whole.Design/methodology/approach:This study utilizes a power law model to explore the relationship between research funding and citations of related papers.The study here analyzes 3,539 recorded documents by Nobel Laureates in physics,chemistry and medicine and a broader dataset of 183,016 documents related to the fields of physics,medicine,and chemistry recorded in the Web of Science database.Findings:Results reveal that in chemistry and medicine,funded researches published in papers of Nobel Laureates have higher citations than unfunded studies published in articles;vice versa high citations of Nobel Laureates in physics are for unfunded studies published in papers.Instead,when overall data of publications and citations in physics,chemistry and medicine are analyzed,all papers based on funded researches show higher citations than unfunded ones.Originality/value:Results clarify the driving role of research funding for science diffusion that are systematized in general properties:a)articles concerning funded researches receive more citations than(un)funded studies published in papers of physics,chemistry and medicine sciences,generating a high Matthew effect(a higher growth of citations with the increase in the number of papers);b)research funding increases the citations of articles in fields oriented to applied research(e.g.,chemistry and medicine)more than fields oriented towards basic research(e.g.,physics).Practical implications:The results here explain some characteristics of scientific development and diffusion,highlighting the critical role of research funding in fostering citations and the expansion of scientific knowledge.This finding can support decision-making of policymakers and R&D managers to improve the effectiveness in allocating financial resources in science policies to generate a higher positive scientific and societal impact.

Target Detection Algorithm in Foggy Scenes Based on Dual Subnets

Under the influence of air humidity,dust,aerosols,etc.,in real scenes,haze presents an uneven state.In this way,the image quality and contrast will decrease.In this case,It is difficult to detect the target in the image by the universal detection network.Thus,a dual subnet based on multi-task collaborative training(DSMCT)is proposed in this paper.Firstly,in the training phase,the Gated Context Aggregation Network(GCANet)is used as the supervisory network of YOLOX to promote the extraction of clean information in foggy scenes.In the test phase,only the YOLOX branch needs to be activated to ensure the detection speed of the model.Secondly,the deformable convolution module is used to improve GCANet to enhance the model’s ability to capture details of non-homogeneous fog.Finally,the Coordinate Attention mechanism is introduced into the Vision Transformer and the backbone network of YOLOX is redesigned.In this way,the feature extraction ability of the network for deep-level information can be enhanced.The experimental results on artificial fog data set FOG_VOC and real fog data set RTTS show that the map value of DSMCT reached 86.56%and 62.39%,respectively,which was 2.27%and 4.41%higher than the current most advanced detection model.The DSMCT network has high practicality and effectiveness for target detection in real foggy scenes.

Electromagnetic pulses produced by a picosecond laser interacting with solid targets

A high-power laser ablating solid targets induces giant electromagnetic pulses(EMPs),which are intimately pertinent to laser parameters,such as energy and pulse width.In this study,we reveal the features of EMPs generated from a picosecond(ps)laser irradiating solid targets at the SG-Ⅱpicosecond petawatt(PSPW)laser facility.The laser energy and pulse,as well as target material and thickness,show determinative effects on the EMPs’amplitude.More intense EMPs are detected behind targets compared to those at the other three positions,and the EMP amplitude decreases from 90.09 kV/m to 17.8 kV/m with the gold target thickness increasing from 10μm to 20μm,which is suppressed when the laser pulse width is enlarged.The results are expected to provide more insight into EMPs produced by ps lasers coupling with targets and lay the foundation for an effective EMP shielding design in high-power laser infrastructures.

Improved Weighted Local Contrast Method for Infrared Small Target Detection

In order to address the problem of high false alarm rate and low probabilities of infrared small target detection in complex low-altitude background,an infrared small target detection method based on improved weighted local contrast is proposed in this paper.First,the ratio information between the target and local background is utilized as an enhancement factor.The local contrast is calculated by incorporating the heterogeneity between the target and local background.Then,a local product weighted method is designed based on the spatial dissimilarity between target and background to further enhance target while suppressing background.Finally,the location of target is obtained by adaptive threshold segmentation.As experimental results demonstrate,the method shows superior performance in several evaluation metrics compared with six existing algorithms on different datasets containing targets such as unmanned aerial vehicles(UAV).

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.