Progress In Basic Research Research Articles

Basic and clinical research progress of AAV-based gene therapy <?A3B2 pi6?>for hereditary deafness

Basic and clinical research progress of AAV-based gene therapy <?A3B2 pi6?>for hereditary deafness

Fiber optic sensing technology in underground pipeline health monitoring: a comprehensive review

Pipelines play a critical role in transporting water, oil, and gas and are indispensable for urban development. However, monitoring underground pipelines is challenging due to the complex environment in which they are situated. Traditional sensors have limitations in all-round and real-time monitoring, while fiber optic sensors offer several advantages, including large coverage, high sensitivity, long sensing distance, and corrosion resistance. As such, fiber optic sensing technology (FOST) has emerged as a promising tool for underground pipeline monitoring. This review article provides a comprehensive overview of FOST, including its basic principles, classification, and research progress in underground pipeline monitoring. Specifically, this article focuses on the technology’s application in monitoring pipeline leakage, deformation, corrosion, and geological natural disasters. In addition, the article highlights the need for future research and development in FOST. For example, combining FOST with artificial intelligence can enhance the accuracy and efficiency of pipeline monitoring. Overall, this review article offers valuable insights into the potential of FOST for underground pipeline monitoring and provides essential guidance for future research in this field.

Progress and prospects in the molecular basic research on important traits in sorghum

Sorghum (Sorghum bicolor) is a significant crop serving food, energy, feed, and industrial raw materials, featuring extensive growth adaptability and diverse utility values. Despite the achievements in sorghum breeding in the last decades, conventional breeding methods still confront challenges such as lengthy breeding cycles, low efficiency, and complex genetic backgrounds. With the rapid advancement of molecular biology, genetics, and bioinformatics, molecular breeding has carved new pathways for enhancing sorghum yield and quality. This article reviews the molecular basic research progress in the key agronomic and adaptive traits of sorghum, including grain yield, grain quality, flowering time, plant height, tillering, stress resistance, and male sterility, and discusses future research priorities, offering novel insights and approaches for sorghum breeding.

Chinese guidelines on the management of hepatic encephalopathy in cirrhosis (2024)

With the progress of basic and clinical research on hepatic encephalopathy in cirrhosis over the world, Chinese Society of Hepatology of the Chinese Medical Association has invited experts in relevant fields to revise the 2018 "Chinese Guidelines on the Management of Hepatic Encephalopathy in Cirrhosis". New guideline provides the recommendations for clinical diagnosis, treatment, primary and secondary prevention of hepatic encephalopathy in cirrhosis.

Advances in the Pathogenesis of Pancreatitis

One of the common acute abdominal diseases of acute pancreatitis, the global incidence of about 34~80 people per 100, 000 people every year, in China and Europe and the United States have been increasing year by year[1]. The common causes of pancreatitis are biliary diseases, alcohol, and hyperlipidemia. Other relatively rare etiologies include drugs, hypercalcemia, split pancreas division, infection, trauma, genetic and autoimmune factors, and many more[2]. However, although the causes of diverse, but it has an important pathophysiological characteristics, namely from the clinical symptoms such as abdominal pain to progress to organ failure such as pancreatitis related lung injury caused by acute respiratory distress syndrome, pancreatitis related renal injury caused by acute renal failure or pancreatic local complications such as pancreatic pseudocyst and so on the pathophysiological process often need several days or even longer. Therefore, clarifying the core molecular events involved in the occurrence and development of acute pancreatitis during this time period can greatly curb the development of pancreatitis. Therefore, this paper will summarize the basic research progress of the pathogenesis of acute pancreatitis in recent years, in order to have clinical guiding significance for the early treatment of acute pancreatitis.

Standardization of next-generation sequencing for detecting mutations associated with targeted therapy and immunotherapy based on dynamic pattern of expandable detection range

Next-generation sequencing (NGS) has laid the foundation for precision oncology care. NGS technologynot only represents an innovation in the methodology but also brings about a revolution in the concept of detecting gene alterations for targeted therapy and immunotherapy of cancers. As basic biomedical research and drug development progress, the landscape of biomarkers associated with gene alterations continues to evolve. Thus, the standardization of NGS-based gene alterations detection should take into account the characteristics of NGS methods and the gene alteration biomarkers. To be specific, whether employed as in vitro diagnostic products or laboratory-developed tests, the detection range can be expanded in response to changes in the clinical evidence level of biomarkers during the process of assay development and clinical application. Such adjustment needs the analytical validation results for supplemented genes or mutant sites within a predefined detection system, which will maximally fulfill the evolving clinical demands in cancer diagnosis and treatment, simultaneously mitigate potential risks effectively. This article primarily discusses the standardization pathway for NGS testing of gene alterations in cancer by focusing on the characteristics of NGS methods, gene alteration biomarkers, and the current status of the standardization of NGS application.

Adipocentric origin of the common cardiometabolic complications of obesity in the young up to the very old: pathophysiology and new therapeutic opportunities.

Obesity is a multifactorial chronic disease characterized by an excess of adipose tissue, affecting people of all ages. In the last 40 years, the incidence of overweight and obesity almost tripled worldwide. The accumulation of "visceral" adipose tissue increases with aging, leading to several cardio-metabolic consequences: from increased blood pressure to overt arterial hypertension, from insulin-resistance to overt type 2 diabetes mellitus (T2DM), dyslipidemia, chronic kidney disease (CKD), and obstructive sleep apnea. The increasing use of innovative drugs, namely glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2-i), is changing the management of obesity and its related cardiovascular complications significantly. These drugs, first considered only for T2DM treatment, are now used in overweight patients with visceral adiposity or obese patients, as obesity is no longer just a risk factor but a critical condition at the basis of common metabolic, cardiovascular, and renal diseases. An adipocentric vision and approach should become the cornerstone of visceral overweight and obesity integrated management and treatment, reducing and avoiding the onset of obesity-related multiple risk factors and their clinical complications. According to recent progress in basic and clinical research on adiposity, this narrative review aims to contribute to a novel clinical approach focusing on pathophysiological and therapeutic insights.

A new era in the science and care of kidney diseases.

Notable progress in basic, translational and clinical nephrology research has been made over the past five decades. Nonetheless, many challenges remain, including obstacles to the early detection of kidney disease, disparities in access to care and variability in responses to existing and emerging therapies. Innovations in drug development, research technologies, tissue engineering and regenerative medicine have the potential to improve patient outcomes. Exciting prospects include the availability of new drugs to slow or halt the progression of chronic kidney disease, the development of bioartificial kidneys that mimic healthy kidney functions, and tissue engineering techniques that could enable transplantable kidneys to be created from the cells of the recipient, removing the risk of rejection. Cell and gene therapies have the potential to be applied for kidney tissue regeneration and repair. In addition, about 30% of kidney disease cases are monogenic and could potentially be treated using these genetic medicine approaches. Systemic diseases that involve the kidney, such as diabetes mellitus and hypertension, might also be amenable to these treatments. Continued investment, communication, collaboration and translation of innovations are crucial to realize their full potential. In addition, increasing sophistication in exploring large datasets, implementation science, and qualitative methodologies will improve the ability to deliver transformational kidney health strategies.

Could nerve transplantation be the future of this field: a bibliometric analysis about lumbosacral plexus injury.

Lumbosacral plexus injury is a highly distressing clinical issue with profound implications for patients' quality of life. Since the publication of the first relevant study in 1953, there has been very limited progress in basic research and clinical treatment in this field, and the developmental trajectory and research priorities in this field have not been systematically summarized using scientific methods, leaving the future direction of this research to be explored. Utilizing publications from the Web of Science (WoS) database, our research employed bibliometric methodology to analyze the fundamental components of publications, synthesize research trends, and forecast future directions. A total of 150 publications were included in our study, and the impressive advancement of research heat in this field can be attributed to the continuous increase in the number of papers, ranging from 14 papers in 2000 to 34 papers in 2023 over five years. Regarding the country, a central position in both quantity (H-index=125) and quality of publications (65 publications) is occupied by the United States, and close collaborations with other countries are observed. In terms of publication institutions, the highest number of publications (9 publications) is held by the Second Military Medical University. The journal with the most publications (5 publications) is the Journal of Trauma-Injury Infection and Critical Care. A pivotal role has been played by basic medical research in the development of this field. Concerning hotspots, the focus of the research core can be divided into three clusters (etiology, diagnosis and treatment; molecular, cells and mechanisms; physiology and pathology). This marks the inaugural bibliometric analysis of lumbosacral plexus injuries, offering a comprehensive overview of current publications. Our findings illuminate future research directions, international collaborations, and interdisciplinary relationships. Future research will emphasize clinical treatment and mechanism research, with a focus on sacral nerve stimulation and nerve transplantation.

RNA m6A Methylation and Alzheimer's Disease: Current Evidence and Future Perspectives

Background: Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by the pathological accumulation of b-amyloid and neurofibrillary tangles. Despite substantial progress in both basic and clinical research on AD, the detailed mechanism of AD pathogenesis is still elusive. RNA N6-methyladenosine methylation (m6A) is the most predominant post-transcriptional modification on eukaryotic mRNA, prominently enriched in the mammalian brain. Notably, m6A-modified RNA showed significant changes during the development of AD, indicating an important role of this modification in AD pathogenesis. Aim: In this study, we aim to provide a summary of recent advances highlighting the indispensable role of m6A in AD pathogenesis. Result: From the perspective of m6A modification, we review our current understanding of the association between RNA m6A machinery and the risk factors of AD, as well as its involvement in various pathophysiological hallmarks of AD. We also discuss the main obstacles in current studies about m6A in AD pathogenesis and the corresponding caveats and solutions to them. Conclusion: This review emphasizes the significance of investigating m6A in the context of AD and highlights the considerable potential for m6A to emerge as a novel therapeutic target for AD.

The Neutrophil-to-Lymphocyte Ratio as a Biomarker in Cutaneous Oncology: A Systematic Review of Evidence beyond Malignant Melanoma.

With the ongoing progress of basic research along with the introduction of new pharmaceutical options spanning almost all therapeutic areas, the need for biomarkers that will be implemented into the personalized medical approach is higher than ever. Their use can be incorporated into clinical practice and can be applied to the classification of disorders and the evaluation of disease severity but also to the monitoring of the progress of therapeutic/pharmaceutical interventions. This systematic review collects the findings of hematologic biomarkers in various cutaneous malignancies, excluding malignant melanoma, to support their potential use in the prognosis but also in the assessment of therapeutic strategies for the specific category of skin disorders.

Landscape of adenosine pathway and immune checkpoint dual blockade in NSCLC: progress in basic research and clinical application.

Lung cancer poses a global threat to human health, while common cancer treatments (chemotherapy and targeted therapies) have limited efficacy. Immunotherapy offers hope of sustained remission for many patients with lung cancer, but a significant proportion of patients fail to respond to treatment owing to immune resistance. There is extensive evidence to suggest the immunosuppressive microenvironment as the cause of this treatment failure. Numerous studies have suggested that the adenosine (ADO) pathway plays an important role in the formation of an immunosuppressive microenvironment and may be a key factor in the development of immune resistance in EGFR-mutant cell lung cancer. Inhibition of this pathway may therefore be a potential target to achieve effective reversal of ADO pathway-mediated immune resistance. Recently, an increasing number of clinical trials have begun to address the broad prospects of using the ADO pathway as an immunotherapeutic strategy. However, few researchers have summarized the theoretical basis and clinical rationale of the ADO pathway and immune checkpoint dual blockade in a systematic and detailed manner, particularly in lung cancer. As such, a timely review of the potential value of the ADO pathway in combination with immunotherapy strategies for lung cancer is warranted. This comprehensive review first describes the role of ADO in the formation of a lung tumor-induced immunosuppressive microenvironment, discusses the key mechanisms of ADO inhibitors in reversing lung immunosuppression, and highlights recent evidence from preclinical and clinical studies of ADO inhibitors combined with immune checkpoint blockers to improve the lung cancer immunosuppressive microenvironment.

Construction and comparison of different vehicles for heterologous gene expression in Zymomonas mobilis.

Zymomonas mobilis has the potential to be an optimal chassis for the production of bulk chemicals derived from pyruvate. However, a lack of available standardized and characterized genetic tools hinders both efficient engineering of Z. mobilis and progress in basic research on this organism. In this study, a series of different shuttle vectors were constructed based on the replication mechanisms of the native Z. mobilis plasmids pZMO1, pZMOB04, pZMOB05, pZMOB06, pZMO7 and p29191_2 and on the broad host range replication origin of pBBR1. These plasmids as well as genomic integration sites were characterized for efficiency of heterologous gene expression, stability without selection and compatibility. We were able to show that a wide range of expression levels could be achieved by using different plasmid replicons. The expression levels of the constructs were consistent with the relative copy numbers, as determined by quantitative PCR. In addition, most plasmids are compatible and could be combined. To avoid plasmid loss, antibiotic selection is required for all plasmids except the pZMO7-based plasmid, which is stable also without selection pressure. Stable expression of reporter genes without the need for selection was also achieved by genomic integration. All modules were adapted to the modular cloning toolbox Zymo-Parts, allowing easy reuse and combination of elements. This work provides an overview of heterologous gene expression in Z. mobilis and adds a rich set of standardized genetic elements to an efficient cloning system, laying the foundation for future engineering and research in this area.

Safeguarding the “Black Soil Granary”: Innovations in Soil Conservation and Sustainable Agriculture

The black soil of northeast China is a “ballast stone” of the nation’s food security and a crucial asset for regional ecological stability. However, it faces severe degradation due to long-term, high-intensity cultivation and soil erosion. To address this issue, the Chinese Academy of Sciences, in collaboration with the three northeastern provinces and Inner Mongolia, launched the “Black Soil Granary” campaign in March 2021. This initiative has achieved phased progress in basic theoretical research, key technology development, equipment fabrication, and technology demonstration. As the campaign continues, innovative technologies, including region-specific models for controlling black soil degradation, methods to enhance both soil health and productivity, and breakthroughs in smart agriculture, are playing a key role in protecting and sustainably utilizing black soils, thus providing strong scientific support for national food security.

Nerve decompression for diabetic peripheral neuropathy with nerve entrapment: a narrative review.

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes which primarily affects the sensory nervous system. Pain is the most common complaint that prompts patients to seek medical advice. With various presentations and intricate pathological mechanisms, diabetic peripheral neuropathic pain is currently the most crucial and challenging aspect of managing diabetic complications. As a heterogeneous disorder, there is no medication or treatment modality that is effective for all types of DPN and its associated neuropathic pain. Peripheral nerve decompression provides a new option for treating patients with diabetic peripheral neuropathic pain in the lower extremities. However, the clinical applicability of nerve decompression has been debated since it was first proposed. This review discusses the theoretical basis of nerve decompression, the clinical indications, and the progress of basic research based on the pathological mechanisms and nerve impairment patterns of diabetic peripheral neuropathic pain. The heterogeneity of DPN patients is summarized in terms of three aspects: complex pathophysiological mechanisms, multilevel nervous system involvement, and various nerve impairment properties. Identifying the presence of nerve entrapment among complex pathophysiological mechanisms is the key to successful outcomes. Tinel signs, focal pain, mechanical allodynia, and two-point discrimination were reported to be prognostic factors for good surgical outcomes, and their predictive ability might stem from their association with the early stage of entrapment neuropathy.

Confined deflagration of propanal/air in the presence of intrinsic instability at elevated pressures

The partial oxidation process is a chemical technique with a high risk of deflagration, which involves directly mixing of fuels with oxidizers at elevated conditions. Under non-standard conditions, the deflagration behaviors of fuels are often unavailable to the general public, which hampers progress in further basic research. In this study, the deflagration behaviors of propanal-air mixtures at 75 °C and 0.1–1.0 MPa were investigated, and the effect of initial pressure (P0) and equivalence ratio (φ) on the deflagration characteristics of propanal was discussed. To explain the similarities and differences in the deflagration characteristics under various conditions, the buoyancy instability, hydrodynamic instability and thermal-diffusion instability suffered by the flames were also analyzed. Results show that the pressure generated by the burned mixture is a cubic function of time, and the state of flame propagation can be determined by the monotonicity of the second-order derivative of pressure. Moreover, the peak deflagration pressure (Pm) is more sensitive to changes in φ on the fuel-lean side, but Pm/P0 at the fuel-rich condition is markedly higher than Pm/P0 at the fuel-lean condition. At all φ, an increase in P0 effectively shortens the ignition time and reduces the minimum ignition energy. Nevertheless, there are discernible differences in the variation patterns of the deflagration time (θm) with P0 at various φ. Specifically, θm gradually prolongs with increasing P0 at fuel-lean conditions, whereas it tends to be the same at different P0 and φ = 1. Furthermore, under fuel-rich conditions, θm progressively shortens as P0 increases. The decrease in θm is attributed to the increasing flame speeds in the presence of intrinsic instability, and the self-accelerating flame yields pressure waves, which travel faster than the flame. Then a series of reflected pressure waves are formed after the pressure waves strike the vessel wall, interacting with the flame front and resulting in the pressure oscillation. Moreover, increasing P0 advances the pressure oscillation and augments the intensity of pressure oscillation.

Myocardial Fibrosis: Emerging Target for Cardiac Molecular Imaging and Opportunity for Image-Guided Therapy.

Myocardial fibrosis is a major contributor to the development and progression of heart failure. Significant progress in the understanding of its pathobiology has led to the introduction and preclinical testing of multiple highly specific antifibrotic therapies. Because the mechanisms of fibrosis are highly dynamic, and because the involved cell populations are heterogeneous and plastic, there is increasing emphasis that any therapy directed specifically against myocardial fibrosis will require personalization and guidance by equally specific diagnostic testing for successful clinical translation. Noninvasive imaging techniques have undergone significant progress and provide increasingly specific information about the quantity, quality, and activity of myocardial fibrosis. Cardiac MRI can precisely map the extracellular space of the myocardium, whereas nuclear imaging characterizes activated fibroblasts and immune cells as the cellular components contributing to fibrosis. Existing techniques may be used in complementarity to provide the imaging biomarkers needed for the success of novel targeted therapies. This review provides a road map on how progress in basic fibrosis research, antifibrotic drug development, and high-end noninvasive imaging may come together to facilitate the success of fibrosis-directed cardiovascular medicine.

Epidermal Growth Factor Receptor-Targeted Neoantigen Peptide Vaccination for the Treatment of Non-Small Cell Lung Cancer and Glioblastoma.

The epidermal growth factor receptor (EGFR) plays crucial roles in several important biological functions such as embryogenesis, epithelial tissue development, and cellular regeneration. However, in multiple solid tumor types overexpression and/or activating mutations of the EGFR gene frequently occur, thus hijacking the EGFR signaling pathway to promote tumorigenesis. Non-small cell lung cancer (NSCLC) tumors in particular often contain prevalent and shared EGFR mutations that provide an ideal source for public neoantigens (NeoAg). Studies in both humans and animal models have confirmed the immunogenicity of some of these NeoAg peptides, suggesting that they may constitute viable targets for cancer immunotherapies. Peptide vaccines targeting mutated EGFR have been tested in multiple clinical trials, demonstrating an excellent safety profile and encouraging clinical efficacy. For example, the CDX-110 (rindopepimut) NeoAg peptide vaccine derived from the EGFRvIII deletion mutant in combination with temozolomide and radiotherapy has shown efficacy in treating EGFRvIII-harboring glioblastoma multiforme (GBM) patients undergone surgery in multiple Phase I and II clinical trials. Furthermore, pilot clinical trials that have administered personalized NeoAg peptides for treating advanced-stage NSCLC patients have shown this approach to be a feasible and safe method to increase antitumor immune responses. Amongst the vaccine peptides administered, EGFR mutation-targeting NeoAgs induced the strongest T cell-mediated immune responses in patients and were also associated with objective clinical responses, implying a promising future for NeoAg peptide vaccines for treating NSCLC patients with selected EGFR mutations. The efficacy of NeoAg-targeting peptide vaccines may be further improved by combining with other modalities such as tyrosine kinase or immune checkpoint inhibitor (ICI) therapy, which are currently being tested in animal models and clinical trials. Herein, we review the most current basic and clinical research progress on EGFR-targeted peptide vaccination for the treatment of NSCLC and other solid tumor types.

Genome Editing for Cystic Fibrosis.

Cystic fibrosis (CF) is a monogenic recessive genetic disorder caused by mutations in the CF Transmembrane-conductance Regulator gene (CFTR). Remarkable progress in basic research has led to the discovery of highly effective CFTR modulators. Now ~90% of CF patients are treatable. However, these modulator therapies are not curative and do not cover the full spectrum of CFTR mutations. Thus, there is a continued need to develop a complete and durable therapy that can treat all CF patients once and for all. As CF is a genetic disease, the ultimate therapy would be in-situ repair of the genetic lesions in the genome. Within the past few years, new technologies, such as CRISPR/Cas gene editing, have emerged as an appealing platform to revise the genome, ushering in a new era of genetic therapy. This review provided an update on this rapidly evolving field and the status of adapting the technology for CF therapy.

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies.

Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted therapy of the p53 signaling pathway is still in its early stages and only a few drugs or treatments have entered clinical trials, the development of new drugs and ongoing clinical trials are expected to lead to the widespread use of p53 signaling-targeted therapy in cancer treatment in the future. TRIAP1 is a novel p53 downstream inhibitor of apoptosis. TRIAP1 is the homolog of yeast mitochondrial intermembrane protein MDM35, which can play a tumor-promoting role by blocking the mitochondria-dependent apoptosis pathway. This work provides a systematic overview of recent basic research and clinical progress in the p53 signaling pathway and proposes that TRIAP1 is an important therapeutic target downstream of p53 signaling.