Current Progress Research Articles

Development in the Inhibition of Dengue Proteases as Drug Targets.

Viral infections continue to increase morbidity and mortality severely. The flavivirus genus has fifty different species, including the dengue, Zika, and West Nile viruses that can infect 40% of individuals globally, who reside in at least a hundred different countries. Dengue, one of the oldest and most dangerous human infections, was initially documented by the Chinese Medical Encyclopedia in the Jin period. It was referred to as "water poison," connected to flying insects, i.e., Aedes aegypti and Aedes albopictus. DENV causes some medical expressions like dengue hemorrhagic fever, acute febrile illness, and dengue shock syndrome. According to the World Health Organization report of 2012, 2500 million people are in danger of contracting dengue fever worldwide. According to a recent study, 96 million of the 390 million dengue infections yearly show some clinical or subclinical severity. There is no antiviral drug or vaccine to treat this severe infection. It can be controlled by getting enough rest, drinking plenty of water, and using painkillers. The first dengue vaccine created by Sanofi, called Dengvaxia, was previously approved by the US-FDA in 2019. All four serotypes of the DENV1-4 have shown re-infection in vaccine recipients. However, the usage of Dengvaxia has been constrained by its adverse effects. Different classes of compounds have been reported against DENV, such as nitrogen-containing heterocycles (i.e., imidazole, pyridine, triazoles quinazolines, quinoline, and indole), oxygen-containing heterocycles (i.e., coumarins), and some are mixed heterocyclic compounds of S, N (thiazole, benzothiazine, and thiazolidinediones), and N, O (i.e., oxadiazole). There have been reports of computationally designed compounds to impede the molecular functions of specific structural and non-structural proteins as potential therapeutic targets. This review summarized the current progress in developing dengue protease inhibitors.

Role of TBK1 Inhibition in Targeted Therapy of Cancer.

TANK-binding kinase 1 (TBK1) is a serine/threonine protein that plays a crucial role in various biological processes like immunity, autophagy, cell survival, and proliferation. The level and kinase activity of the TBK1 protein is regulated through post-translational modifications (PTMs). TBK1 mainly mediates the activation of IRF3/7 and NF-κB signaling pathways while also participating in the regulation of cellular activities such as autophagy, mitochondrial metabolism, and cell proliferation. TBK1 regulates immune, metabolic, inflammatory, and tumor occurrence and development within the body through these cellular activities. TBK1 kinase has emerged as a promising therapeutic target for tumor immunity. However, its molecular mechanism of action remains largely unknown. The identification of selective TBK1 small molecule inhibitors can serve as valuable tools for investigating the biological function of TBK1 protein and also as potential drug candidates for tumor immunotherapy. The current research progress indicates that some TBK1 inhibitors (compounds 15,16 and 21) exhibit certain antitumor effects in vitro culture systems. Here, we summarize the mechanism of action of TBK1 in tumors in recent years and the progress of small molecule inhibitors of TBK1.

Unlocking the Potential of RNA Nanoparticles: A Breakthrough Approach to Overcoming Challenges in Colon Cancer Treatment.

Globally, one of the leading causes of cancer-related deaths is colon cancer. As this form of cancer has a tremendous potential to metastasize, effective treatment is complicated and sometimes impossible. Despite the improvement of conventional chemotherapy and the advent of targeted therapies, overcoming multi-drug resistance (MDR) and side effects remain significant challenges. As a therapeutic intervention for targeted gene silencing in cancer, RNA technology shows promise and certain RNA-based formulations are currently undergoing clinical studies. Various studies have reported that RNA-based nanoparticles have demonstrated substantial promise for targeted medication delivery, gene therapy, and other biomedical applications. However, using RNA as a therapeutic tool presents severe limitations, mainly related to its low stability and poor cellular uptake. Nanotechnology offers a flexible and tailored alternative due to the difficulties in delivering naked RNA molecules safely in vivo, such as their short half-lives, low chemical stability, and susceptibility to nuclease degradation. In addition to shielding RNA molecules from immune system attacks and enzymatic breakdown, the nanoparticle-based delivery systems allow RNA accumulation at the tumor site. The potential of RNA and RNA-associated nanomedicines for the treatment of colon cancer, as well as the prospects for overcoming any difficulties related to mRNA, are reviewed in this study, along with the current progress of mRNA therapeutics and advancements in designing nanomaterials and delivery strategies.

Interfacial Solar Evaporation: From Fundamental Research to Applications.

In the last decade, interfacial solar steam generation (ISSG), powered by natural sunlight garnered significant attention due to its great potential for low-cost and environmentally friendly clean water production in alignment with the global decarbonization efforts. This review aims to share the knowledge and engage with a broader readership about the current progress of ISSG technology and the facing challenges to promote further advancements toward practical applications. The first part of this review assesses the current strategies for enhancing the energy efficiency of ISSG systems, including optimizing light absorption, reducing energy losses, harvesting additional energy, and lowering evaporation enthalpy. Subsequently, the current challenges faced by ISSG technologies, notably salt accumulation and bio-fouling issues in practical applications, are elucidated and contemporary methods are discussed to overcome these challenges. In the end, potential applications of ISSG, ranging from initial seawater desalination and industrial wastewater purification to power generation, sterilization, soil remediation, and innovative concept of solar sea farm, are introduced, highlighting the promising potential of ISSG technology in contributing to sustainable and environmentally conscious practices. Based on the review and in-depth understanding of these aspects, the future research focuses are proposed to address potential issues in both fundamental research and practical applications.

Current progress and future perspectives in total‐body PET imaging, part I: Data processing and analysis

AbstractTotal‐body positron emission tomography (TB‐PET) has ultra‐high sensitivity and the unique ability to conduct dynamic imaging of the entire body. Both the hardware configuration and the data acquired from a TB‐PET scanner differ from those of the conventional short axial field‐of‐view scanners. Therefore, various aspects concerning data processing need careful consideration when implementing TB‐PET in clinical settings. Additionally, advances in data analysis are needed to fully uncover the potential of these systems. Although some progress has been achieved, further research and innovation in scan data management are necessary. In this report, we provide a comprehensive overview of the current progress, challenges, and possible future directions for TB‐PET data processing and analysis. For a review of clinical applications, please find the other review accompanying this paper.

Research Progress on Spatiotemporal Interpolation Methods for Meteorological Elements

With the development of mathematical statistics, people have developed the spatiotemporal interpolation methods based on the spatial interpolation method or the temporal interpolation method. These methods fully consider the comprehensive effects of time series changes and spatial distribution to better handle complicated and changeable meteorological element data. This article systematically reviews the current research progress of spatiotemporal interpolation methods for spatiotemporal sampling data of meteorological origin. Spatiotemporal interpolation methods of meteorological elements are classified into three categories: spatiotemporal geostatistical interpolation methods, spatiotemporal deterministic interpolation methods, and spatiotemporal mixed interpolation methods. This article summarizes the theoretical concept and practical application of the spatiotemporal interpolation methods of meteorological elements, analyzes the advantages and disadvantages of using spatiotemporal interpolation methods for estimating or forecasting meteorological elements, combined through some measures and their application to explain the accuracy of the spatiotemporal interpolation methods; and discusses the problems and challenges of spatiotemporal interpolation. Finally, the future research focus of spatiotemporal interpolation methods is proposed. This article provides a valuable method reference for estimating or predicting meteorological elements such as precipitation in unsampled points.

Physician Workforce Diversity Is Still Necessary and Achievable if It Is Intentionally Prioritized.

The 2023 Supreme Court Decision from Students for Fair Admissions v. Harvard and Students for Fair Admissions v. University of North Carolina threatens the current progress in achieving diversity within undergraduate and graduate medical education. This is necessary to achieve a diverse healthcare workforce, which is a key to healing historical healthcare trauma, eliminating health disparities, and providing equitable healthcare access for all communities. Although the Supreme Court decision seems obstructionist, viable opportunities exist to enhance recruitment further and solidify diversity efforts in undergraduate and graduate medical education to achieve these goals.

A Perspective on the Molecular Modeling of Electrolyte Decomposition Reactions for Solid Electrolyte Interphase Growth in Lithium‐Ion Batteries

AbstractThe solid electrolyte interphase (SEI) is a thin heterogeneous layer formed at the anode/electrolyte interface in lithium‐ion batteries as a consequence of the reduction of the electrolyte. The initial formation of the SEI inhibits the direct contact between the electrode and the electrolyte and thus protects the battery. However, the composition, structure, and size of the SEI evolve over time and the growth of the SEI is considered the primary mechanism leading to the gradual deterioration of the battery performance. Despite the importance of the SEI and its growth, the atomistic understanding of the underlying elementary reaction steps remains partial. Molecular modeling of the electrolyte decomposition is key to gain detailed insights that are complementary to experiments for the reactions occurring in this heterogenous interphase. In this perspective, the electron transport mechanisms are first described from the anode to the electrolyte through the SEI and highlight the importance of the inorganic/organic interface within the heterogeneous SEI: it is where the electrolyte decomposition reactions are likely to occur. Finally, a view is provided on the current progress on molecular modeling techniques (e.g., Density Functional Theory, force fields, machine learning potentials) of the SEI and the challenges each method faces.

Flexible Supercapacitor Integrated Systems

AbstractThere is a pressing need for flexible integrated systems owing to the swift progress of flexible electronics. Apart from flexibility, flexible supercapacitor (FSC) integrated systems exhibit certain characteristics like rapid charge–discharge rates, high power density, and excellent cycling stability, which makes them a promising candidate to serve as a vital component in flexible electronics. In this context, an in‐depth overview of recent progress in FSC‐integrated systems, including their design of structure, materials, fabrication techniques, and applications, is offered. On the basis of the current progress, the existing challenges and future prospects are also outlined and discussed.

Current progress and future perspectives in total‐body positron emission tomography/computed tomography. Part II: Clinical applications

AbstractTotal‐body positron emission tomography (TB‐PET) has significantly advanced from initial conception to global commercial availability. The high sensitivity of TB‐PET has led to superior lesion detection, thereby expanding the range of clinical applications. TB‐PET technology offers several advantages: (a) It enables the detection of small lesions, facilitating precise cancer staging and targeted cancer formulation. (b) The technology shortens the acquisition time while maintaining the quality of diagnostic images. (c) TB‐PET allows for a reduction in the amount of administered radiotracer, which minimizes image noise, reduces the effective radiation dose to patients, and enhances staff safety. (d) The scanner supports the development of new tracers and the dynamic imaging of these tracers throughout the entire body. (e) TB‐PET accommodates delayed scanning, which has been shown to improve the detection of small and previously undetected malignant lesions by enhancing the clearance in areas of significant background activity. (f) Owing to its high‐quality images, TB‐PET is suitable for parametric imaging, which offers several advantages over conventional standardized uptake value imaging. However, TB‐PET still faces several challenges. There is a lack of consensus on the optimal dose and scan duration for clinical diagnosis using TB‐PET. Additionally, unified standards for parametric imaging via TB‐PET are yet to be established, and the full clinical significance of this technology remains under‐explored. The accompanying review (Part 1) covers TB‐PET data manipulation and analysis.

Health-related quality of life in patients with hematologic malignancies treated with chimeric antigen receptor T-cell therapy: review and current progress.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the care of patients with relapsed/refractory B-cell derived hematologic malignancies. To date, six CAR T-cell therapies, targeting either CD19 or B-cell maturation antigen, have received regulatory approval. Along with the promising survival benefit, CAR T-cell therapy is associated with potentially lifethreatening adverse events (AE), including cytokine release syndrome and immune effector cellassociated neurotoxicity syndrome. While clinical trials evaluating CAR T-cell therapy consistently report the incidence of these AE, most trials do not collect health-related quality of life (HRQoL) data. As such, the impact of CAR T-cell therapy process and related AE on the physical and psychological well-being of patients remains uncertain. HRQoL and other patientreported outcome (PRO) assessments in patients with relapsed or refractory hematologic malignancies are of utmost importance, as individuals may have unmet needs and a high demand for tolerable therapy if a cure is not obtained. In addition, it is important to standardize methods of data collection to better assess the impact of CAR T-cell therapy on quality of life, optimize patient care and costs, and enable comparison between different studies. We conducted a literature search up to June 2023 to identify the HRQoL tools used in clinical trials and in realworld studies investigating CAR T-cell therapy in patients with lymphomas or leukemias. In the present comprehensive review, we summarize the most commonly used CAR T-cell specific and non-specific HRQoL tools and discuss how the use of HRQoL and other PRO tools may be optimized.

Research advances in Peyronie's disease: a comprehensive review on genomics, pathways, phenotypic manifestation, and therapeutic targets.

Penile induration disease, commonly known as Peyronie's disease (PD), is a connective tissue disorder that affects the penis, leading to the development of fibrous plaques, penile curvature, and erectile dysfunction. PD is a common male reproductive system disease with a complex etiology involving multiple genes, signaling pathways, and different phenotypes. The etiology and pathogenesis of PD remain poorly understood, hindering the development of effective treatment strategies. By understanding the underlying mechanisms of PD, we can pave the way for targeted therapies and improved patient outcomes. We reviewed the epidemiology and pathophysiology of PD. We performed database searches on Google Scholar, PubMed, Medline, and Web of Science from inception to September 2023. The literature reviewed included priapism guidelines, review articles, current trial studies, and various literature related to PD. This article provides a comprehensive overview of the current research progress on the disease, focusing on its genetic factors, signaling pathways, cellular mechanisms, phenotypic manifestations, and therapeutic targets. It can help identify individuals at higher risk, aid in early detection and intervention, and provide insights into fibrosis and tissue remodeling. It can also reveal potential therapeutic targets, guide accurate diagnoses and treatment strategies, and address the impact of the disease on patients' quality of life. By integrating insights from genomics, molecular pathways, clinical phenotypes, and therapeutic potentials, our research aims to achieve a deeper and more comprehensive understanding of PD, propelling the field toward innovative strategies that enhance the lives of those affected by PD. The complex manifestations and pathogenesis of PD necessitate the use of multiple treatment methods for personalized care.

Drug resistance and therapeutic advances in Treponema pallidum: A review

Treponema pallidum, a common pathogen in sexually transmitted diseases, has emerged as a significant public health threat in recent decades, showing a gradual increase in global prevalence. Antibiotics have been the primary method to treat Treponema pallidum infections. However, high-dose antibiotic use in clinical trials has raised concerns and unveiled a series of issues. This paper employs a literature review approach to summarize and compare scientific studies conducted in various countries and regions regarding Treponema pallidum in recent years. It aims to introduce and summarize the drug resistance of Treponema pallidum and the current progress in treatment. Studies indicate widespread resistance of Treponema pallidum to macrolides, while no resistance has been found to first-line drugs like benzathine penicillin and other alternative medications. Presently, benzathine penicillin remains pivotal in syphilis treatment. Alternatives such as ceftriaxone, second-generation tetracyclines, amoxicillin, and adjunctive immunomodulators, after clinical trials, have been used in early or late-stage syphilis treatment and prevention. The concept and research direction of syphilis vaccines are emerging and are poised to be a crucial approach in curtailing Treponema pallidum transmission. Diversified drug treatment strategies and the development of syphilis vaccines hold significant implications in safeguarding public health and ensuring global health security.

Immunotherapy of Human Melanoma: Past, Present, Future.

Immunotherapy with immune checkpoint inhibitors (ICIs) is a promising therapeutic schedule in advanced solid cancers. In this review, clinical trials from highly reputable journals are interpreted for safety and efficacy evaluation of the common anti-programmed death-1 (PD-1) inhibitor nivolumab and/or the most known anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitor ipilimumab in advanced melanoma. Current progress in the field of melanoma immunotherapy is the focus of this review. Solo nivolumab and combo nivolumab-ipilimumab show higher responses compared to solo ipilimumab or chemotherapy. BRAF and programmed death-ligand 1 (PDL1) expression states are seemingly not reliable biomarkers of response to ICI therapy in melanoma. Solo ipilimumab and particularly a combination of nivolumab-ipilimumab show higher adverse events (AEs) compared with solo nivolumab or chemotherapy. Besides, ICI therapy is safer in mucosal melanoma, but its efficacy is higher in the cutaneous subtype. Patients receiving combination regimens who are experiencing serious AEs can discontinue such regimens until recovery and still maintain clinical benefits. To conclude, combo nivolumab-ipilimumab represents more therapeutic advantages compared with solo nivolumab or ipilimumab, but the rate of AEs is higher for combination regimens. Resistance to combo nivolumab-ipilimumab demands the application of novel approaches to go with ICIs in melanoma immunotherapy. Immunogenic agents, alternative immune checkpoints, vaccination, oncolytic viruses, extracellular vesicles (EVs) and fecal microbiome transplantation (FMT) are novel strategies in patients developing ICI resistance.

Current research progress of whole genome sequencing in practical

Gene sequencing, a vital technique nowadays, detects patients diseases and helping with diagnosis. Whole genome sequencing (WGS) is one member of this family, which mainly functions in analysing participants gene sequences in clinical diagnosis for the purpose of indicating therapeutic interventions. This essay compares WGS and other sequencing methods, such as whole exome sequencing (WES), which comprises both positive and negative sides of this sequencing test for evaluation. And point out the help of WGS in certain diseases. This paper serves as a synopsis of some WGS-related themes as well as potential directions in the future for technical advancement.

A 3D-Printed Scaffold for Repairing Bone Defects.

The treatment of bone defects has always posed challenges in the field of orthopedics. Scaffolds, as a vital component of bone tissue engineering, offer significant advantages in the research and treatment of clinical bone defects. This study aims to provide an overview of how 3D printing technology is applied in the production of bone repair scaffolds. Depending on the materials used, the 3D-printed scaffolds can be classified into two types: single-component scaffolds and composite scaffolds. We have conducted a comprehensive analysis of material composition, the characteristics of 3D printing, performance, advantages, disadvantages, and applications for each scaffold type. Furthermore, based on the current research status and progress, we offer suggestions for future research in this area. In conclusion, this review acts as a valuable reference for advancing the research in the field of bone repair scaffolds.

Roadmap for Clinical Translation of Mobile Microrobotics.

Medical microrobotics is an emerging field to revolutionize clinical applications in diagnostics and therapeutics of various diseases. On the other hand, the mobile microrobotics field has important obstacles to pass before clinical translation. This article focuses on these challenges and provides a roadmap of medical microrobots to enable their clinical use. From the concept of a "magic bullet" to the physicochemical interactions of microrobots in complex biological environments in medical applications, there are several translational steps to consider. Clinical translation of mobile microrobots is only possible with a close collaboration between clinical experts and microrobotics researchers to address the technical challenges in microfabrication, safety, and imaging. The clinical application potential can be materialized by designing microrobots that can solve the current main challenges, such as actuation limitations, material stability, and imaging constraints. The strengths and weaknesses of the current progress in the microrobotics field are discussed and a roadmap for their clinical applications in the near future isoutlined.

Advancements in solvent microextraction: Recent developments and diverse applications in the modern era

AbstractSolvent microextraction (SME) is designed to selectively isolate desired analytes while minimizing the presence of interfering substances in the extracted sample. There are different approaches from which single‐drop microextraction (SDME) can be amalgamated with various analytical methods to enhance its functionalities and improve the analysis of extracted compounds like gas chromatography, and liquid chromatography amplify sensitivity, selectivity, and the capacity to detect trace amounts of analytes in complex matrices. The review focuses on the intricacies of solid‐phase microextraction and elucidates its operational principles. Additionally, it explores various types of SDMEs, detailing their respective benefits, drawbacks, and potential applications in the future. A typical explanation of the construction and working of hollow fiber‐liquid phase microextraction as well as its types has been discussed. The applications of SMEs in the medical and biomedical fields from food analysis to environmental analysis like analysis and purification of water, organic pollutants, drug analysis, and screening of new drugs have been discussed and also illustrated in tabular form. The pros and cons of both analytical techniques are given in a tabular manner as well a broad comparison between different types of advanced SME techniques provides a new direction for environmental monitoring, food safety, and refining of impurities from water samples. The review provides a comprehensive overview of the current progress, recent obstacles, and future possibilities of SMEs in an appropriate manner. Despite numerous promising advancements, the utilization of SMEs remains a challenging field.

Photocatalytic methane conversion to high-value chemicals

Methane has a substantial and widespread reserve on Earth. As a very abundant carbon and hydrogen source, as well as an energy vector, upgrading methane to higher-value fuels and chemicals (carbon oxygenates, C₂₊ hydrocarbons, et al.) is a promising technology in the supply of energy and chemicals by a low-carbon process. Due to the stable and inert nature of methane, activating and converting the molecule is extremely challenging. Currently, commercial methane conversion technology operates at high temperatures and/or high pressure, suffering from intense energy consumption and high capital investment. Photocatalysis, using photons as the only energy input, can operate at mild temperatures and under atmospheric pressure, which is a promising and green technology for methane conversion to highvalue products. In this review, fundamental understandings of photocatalytic methane activation and product yield involving different oxidants are discussed. Then recent advances in photocatalysts for methane conversion to hydrocarbons and oxygenates are detailed, including the relevant reaction mechanism and reaction pathways. Finally, the challenges and perspectives for photocatalytic methane conversion will be discussed based on the current progress and fundamental understanding.

An Assessment of Solar Cycle 25 progress through observation of SRBs and associated Geomagnetic Storms

Geomagnetic storms are severe aspects of Space Weather. They originate due to solar transient emissions such as coronal mass ejections (CMEs), whose energetic materials propagate in the Interplanetary medium and are coupled with the magnetosphere system. CME driven Geomagnetic storms are often associated with solar radio bursts (SRBs), particularly type II and type IV bursts. In this study, we present the preliminary results of solar radio observations and their associated geomagnetic activity during solar cycle 25 (SC 25) from January 2020 to June 2023, focusing on the cycle’s first four intense geomagnetic storms. The study used various radio telescopes, mainly the compound astronomical low-frequency low-cost instrument for spectroscopy and transportable observatory (CALLISTO), as well as OMNI data and the World Data Center for Geomagnetism. During the study period, it was found that 23 solar radio bursts diagnosed the geomagnetic storms with Dst <-50nT from 35 reported, including three severe storms of the SC 25. The time delay between the solar radio bursts and the arrival of CMEs and/or HSS near the Earth’s magnetosphere is estimated with an average value of 79 h within the [48–120 h] range for 23 geomagnetic storms associated with solar radio bursts. Among 35 geomagnetic storms recorded, five are recurring geomagnetic storms associated with coronal high-speed streams (HSS), while CMEs cause the rest with average speeds of 750 km/s. The current SC 25 recognizes four major storms within the scope of the study. On 21 April 2023, a type II radio burst followed by a type IV burst diagnosed the first severe geomagnetic storm on 24 April 2023. The second severe storm was unusual and detected in the absence of the precursor as a solar radio burst. The SRBs of type II burst and type IV burst extending in IP medium on 1 November 2021 tracked the third major storm of the cycle while the group of type III radio bursts, type II and type IV bursts on 24 February 2023, predicted the major storm on 27 February 2023. These major geomagnetic storms are linked to CMEs that show expanding flux ropes, which are signatures of type II and moving type IV radio bursts identified. Furthermore, the detected SRBs and related major geomagnetic storms are proof of high solar and magnetic activity of the ascending phase of SC 25. The SC 25 has been characterized overall, and its current progress is being tracked using observations of SRBs and magnetic activity during its rising phase.