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Latest Issue
Volume 12 ， Issue 5 ， 2025
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Crisis in the gut: navigating gastrointestinal challenges in Gulf War Illness with bioengineering AI Introduction
“Reporting on the latest research advancements, the study delves into the mechanisms behind gastrointestinal disorders in Gulf War Illness, revealing that neuroinflammation alters gut motility and drives symptoms. Expert insights suggest in vitro bioengineering models could be pivotal in understanding and treating GWI-related gastrointestinal pathology.”
Abstract：Gulf War Illness (GWI) is characterized by a wide range of symptoms that manifests largely as gastrointestinal symptoms. Among these gastrointestinal symptoms, motility disorders are highly prevalent, presenting as chronic constipation, stomach pain, indigestion, diarrhea, and other conditions that severely impact the quality of life of GWI veterans. However, despite a high prevalence of gastrointestinal impairments among these veterans, most research attention has focused on neurological disturbances. This perspective provides a comprehensive overview of current in vivo research advancements elucidating the underlying mechanisms contributing to gastrointestinal disorders in GWI. Generally, these in vivo and in vitro models propose that neuroinflammation alters gut motility and drives the gastrointestinal symptoms reported in GWI. Additionally, this perspective highlights the potential and challenges of in vitro bioengineering models, which could be a crucial contributor to understanding and treating the pathology of gastrointestinal related-GWI.Keywords：Gulf War Illness (GWI);Bioengineering;Neuroimmune crosstalk;Gastrointestinal motility67|2|0Updated：2025-12-13
PERSPECTIVE
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PANX1-mediated ATP release confers FAM3A’s suppression effects on hepatic gluconeogenesis and lipogenesis AI Introduction
“In a groundbreaking study, researchers unveil the pivotal role of PANX1-mediated ATP release in maintaining hepatic glucolipid homeostasis, shedding light on FAM3A's suppressive effects on hepatic gluconeogenesis and lipogenesis.”
Abstract：Background:Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet β cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed.Methods:db/db, high-fat diet (HFD)-fed, and global pannexin 1 (PANX1) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein–protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays.Results:In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased (P<0.01). Hepatic PANX1 overexpression ameliorated the dysregulated glucolipid metabolism in obese mice. Mice with hepatic PANX1 knockdown or global PANX1 knockout exhibited disturbed glucolipid metabolism. Restoration of hepatic PANX1 rescued the metabolic disorders of PANX1-deficient mice (P<0.05). Mechanistically, ATP release is mediated by the PANX1-activated protein kinase B-forkhead box protein O1 (Akt-FOXO1) pathway to inhibit gluconeogenesis via P2Y receptors in hepatocytes. PANX1-mediated ATP release also activated calmodulin (CaM) (P<0.01), which interacted with c-Jun N-terminal kinase (JNK) to inhibit its activity, thereby deactivating the transcription factor activator protein-1 (AP1) and repressing fatty acid synthase (FAS) expression and lipid synthesis (P<0.05). FAM3A stimulated the expression of PANX1 via heat shock factor 1 (HSF1) in hepatocytes (P<0.05). Notably, FAM3A overexpression failed to promote ATP release, inhibit the expression of gluconeogenic and lipogenic genes, and suppress gluconeogenesis and lipid deposition in PANX1-deficient hepatocytes and livers.Conclusions:PANX1-mediated release of ATP plays a crucial role in maintaining hepatic glucolipid homeostasis, and it confers FAM3A’s suppressive effects on hepatic gluconeogenesis and lipogenesis.Keywords：Pannexin 1 (PANX1);Family with sequence similarity 3 member A (FAM3A);Adenosine triphosphate (ATP) release;Glucolipid metabolism35|0|0Updated：2025-12-13 - “In the field of Parkinson's disease treatment, researchers have made significant progress. They found that transforming growth factor-β1 (TGF-β1) secreted from hypoxia-preconditioned olfactory mucosa-mesenchymal stem cells (hOM-MSCs) plays a critical role in modulating mitochondrial function recovery in dopaminergic neurons, providing a new direction for PD research.”
Abstract：Background:Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear.Methods:We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase Ⅰ firstin-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients.Results:A functional assay identified that transforming growth factor-β1 (TGF-β1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD.Conclusions:These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.Keywords：Parkinson’s disease (PD);Hypoxia-preconditioned;Olfactory mucosa mesenchymal stem cells (OM-MSCs);Transforming growth factor-β1 (TGF-β1);Microglia;PI3K/Akt signaling pathway;Immune regulation;Autophagy28|0|0Updated：2025-12-13 -
Poor sleep and decreased cortical thickness in veterans with mild traumatic brain injury and post-traumatic stress disorder AI Introduction
“In a recent study, researchers at VA Boston, MA, investigated the relationship between sleep quality and brain volume changes in veterans, particularly those with mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). The study found that poor sleep quality is significantly associated with decreased cortical thickness in veterans with mTBI, either alone or comorbid with PTSD, primarily within frontal regions. This finding may have important implications for the treatment of veterans who have sustained mTBI.”
Abstract：Background:Poor sleep quality has been associated with changes in brain volume among veterans, particularly those who have experienced mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). This study sought to investigate: 1) whether poor sleep quality is associated with decreased cortical thickness in Iraq and Afghanistan war veterans, and 2) whether these associations differ topographically depending on the presence or absence of mTBI and PTSD.Methods:A sample of 440 post-9/11 era U.S. veterans enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders study at VA Boston, MA from 2010 to 2022 was included in the study. We examined the relationship between sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), and cortical thickness in veterans with mTBI (n=57), PTSD (n=110), comorbid mTBI and PTSD (n=129), and neither PTSD nor mTBI (n=144). To determine the topographical relationship between subjective sleep quality and cortical thickness in each diagnostic group, we employed a General Linear Model (GLM) at each vertex on the cortical mantle. The extent of topographical overlap between the resulting statistical maps was assessed using Dice coefficients.Results:There were no significant associations between PSQI and cortical thickness in the group without PTSD or mTBI (n=144) or in the PTSD-only group (n=110). In the mTBI-only group (n=57), lower sleep quality was significantly associated with reduced thickness bilaterally in frontal, cingulate, and precuneus regions, as well as in the right parietal and temporal regions (β=–0.0137, P<0.0005). In the comorbid mTBI and PTSD group (n=129), significant associations were observed bilaterally in frontal, precentral, and precuneus regions, in the left cingulate and the right parietal regions (β=–0.0094, P<0.0005). Interaction analysis revealed that there was a stronger relationship between poor sleep quality and decreased cortical thickness in individuals with mTBI (n=186) compared with those without mTBI (n=254) specifically in the frontal and cingulate regions (β=–0.0077, P<0.0005).Conclusions:This study demonstrates a significant relationship between poor sleep quality and lower cortical thickness primarily within frontal regions among individuals with both isolated mTBI or comorbid diagnoses of mTBI and PTSD. Thus, if directionality is established in longitudinal and interventional studies, it may be crucial to consider addressing sleep in the treatment of veterans who have sustained mTBI.Keywords：Trauma;Brain injury;Sleep;Veterans;Cortical thickness23|0|0Updated：2025-12-13 - “Reporting on the latest research, experts have established the National Disease Surveillance Points system, which explores age-specific temporal trends in mortality for cervical and breast cancers in urban and rural areas of China from 2009 to 2021. This study provides solutions to address rural-urban disparities in cancer control programs and promotes health equity.”
Abstract：Background:Cervical and breast cancers are among the top 4 leading causes of cancer-related mortality in women. This study aimed to examine age-specific temporal trends in mortality for cervical and breast cancers in urban and rural areas of China from 2009 to 2021.Methods:Age-specific mortality data for cervical and breast cancers among Chinese women aged 20–84 years were obtained from China’s National Disease Surveillance Points system spanning the years 2009 to 2021. Negative binomial regression models were utilized to assess urban-rural differences in mortality rate ratios, while Joinpoint models with estimated average annual percent changes (AAPC) and slopes were employed to compare temporal trends and the acceleration of mortality rates within different age groups.Results:From 2009 to 2021, there was a relative increase in age-specific mortality associated with the two cancers observed in rural areas compared with urban areas. A rising trend in the screening age of 35–64 [AAPC: 4.0%, 95% confidence interval (CI) 0.5–7.6, P=0.026] for cervical cancer was noted in rural areas, while a stable trend (AAPC: –0.7%, 95% CI –5.8 to 4.6, P=0.780) was observed in urban areas. As for breast cancer, a stable trend (AAPC: 0.3%, 95% CI –0.3 to 0.9, P=0.280) was observed in rural areas compared to a decreasing trend (AAPC: –2.7%, 95% CI –4.6 to –0.7, P=0.007) in urban areas. Urban-rural differences in mortality rates increased over time for cervical cancer but decreased for breast cancer. Mortality trends for both cervical and breast cancers showed an increase with age across 4 segments, with the most significant surge in mortality observed among the 35–54 age group across urban and rural areas, periods, and regions in China.Conclusions:Special attention should be given to women aged 35–54 years due to mortality trends and rural–urban disparities. Focusing on vulnerable age groups and addressing rural–urban differences in the delivery of cancer control programs can enhance resource efficiency and promote health equity.Keywords：cervical cancer;Breast cancer;Age-specific mortality;Trend;Urban–rural difference;Joinpoint model;China22|0|0Updated：2025-12-13
RESEARCH
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Digital in-line holographic microscopy for label-free identification and tracking of biological cells AI Introduction
“Digital in-line holographic microscopy (DIHM), a non-invasive, real-time, label-free technique, captures 3D positional, orientational, and morphological information from living biological cells. This review outlines the fundamental principles and comprehensive digital image processing procedures employed in DIHM-based cell tracking methods. Leveraging artificial intelligence has significantly enhanced both the speed and accuracy of digital image processing for cell tracking and identification, which provides solutions to solve problems in label-free identification and digital tracking of various motile biological cells.”
Abstract：Digital in-line holographic microscopy (DIHM) is a non-invasive, real-time, label-free technique that captures three-dimensional (3D) positional, orientational, and morphological information from digital holographic images of living biological cells. Unlike conventional microscopies, the DIHM technique enables precise measurements of dynamic behaviors exhibited by living cells within a 3D volume. This review outlines the fundamental principles and comprehensive digital image processing procedures employed in DIHM-based cell tracking methods. In addition, recent applications of DIHM technique for label-free identification and digital tracking of various motile biological cells, including human blood cells, spermatozoa, diseased cells, and unicellular microorganisms, are thoroughly examined. Leveraging artificial intelligence has significantly enhanced both the speed and accuracy of digital image processing for cell tracking and identification. The quantitative data on cell morphology and dynamics captured by DIHM can effectively elucidate the underlying mechanisms governing various microbial behaviors and contribute to the accumulation of diagnostic databases and the development of clinical treatments.Keywords：Digital in-line holographic microscopy (DIHM);Cell identification;Cell tracking;Artificial intelligence21|0|0Updated：2025-12-13 -
Role of signaling pathways in age-related orthopedic diseases: focus on the fibroblast growth factor family AI Introduction
“Reporting on the latest research, the paper delves into the role of fibroblast growth factor (FGF) signaling in orthopedic diseases, highlighting its regulation of cartilage and bone health. Expert research has identified potential FGF signaling targets, paving the way for future therapeutic strategies to combat conditions like osteoarthritis and osteoporosis.”
Abstract：Fibroblast growth factor (FGF) signaling encompasses a multitude of functions, including regulation of cell proliferation, differentiation, morphogenesis, and patterning. FGFs and their receptors (FGFR) are crucial for adult tissue repair processes. Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage, bone loss, muscle reduction, and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis (OA), intervertebral disc degeneration (IVDD), osteoporosis (OP), and sarcopenia. In OA and IVDD pathologies specifically, FGF1, FGF2, FGF8, FGF9, FGF18, FGF21, and FGF23 regulate the synthesis, catabolism, and ossification of cartilage tissue. Additionally, the dysregulation of FGFR expression (FGFR1 and FGFR3) promotes the pathological process of cartilage degradation. In OP and sarcopenia, endocrine-derived FGFs (FGF19, FGF21, and FGF23) modulate bone mineral synthesis and decomposition as well as muscle tissues. FGF2 and other FGFs also exert regulatory roles. A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration. Moreover, an increasing number of potential targets within the FGF signaling have been identified, such as FGF9, FGF18, and FGF23. However, it should be noted that most of these discoveries are still in the experimental stage, and further studies are needed before clinical application can be considered. Presently, this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases. Besides, current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.Keywords：Fibroblast growth factor (FGF);Fibroblast growth factor receptor (FGFR);Osteoarthritis (OA);Intervertebral disc degeneration (IVDD);Orthopedic degeneration;Osteoporosis (OP);Sarcopenia23|1|0Updated：2025-12-13
REVIEW
- “In the realm of healthcare data analysis, a new guidance system for algorithm development has been introduced. Expert researchers have established the DEVELOP-RCD system, which offers a standardized workflow and 13 recommendations for accurately identifying health conditions from routinely collected data. This advancement lays a foundation for enhancing the credibility of observational studies.”
Abstract：Background:In recent years, there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data (RCD). These studies rely on algorithms to identify specific health conditions (e.g., diabetes or sepsis) for statistical analyses. However, there has been substantial variation in the algorithm development and validation, leading to frequently suboptimal performance and posing a significant threat to the validity of study findings. Unfortunately, these issues are often overlooked.Methods:We systematically developed guidance for the development, validation, and evaluation of algorithms designed to identify health status (DEVELOP-RCD). Our initial efforts involved conducting both a narrative review and a systematic review of published studies on the concepts and methodological issues related to algorithm development, validation, and evaluation. Subsequently, we conducted an empirical study on an algorithm for identifying sepsis. Based on these findings, we formulated specific workflow and recommendations for algorithm development, validation, and evaluation within the guidance. Finally, the guidance underwent independent review by a panel of 20 external experts who then convened a consensus meeting to finalize it.Results:A standardized workflow for algorithm development, validation, and evaluation was established. Guided by specific health status considerations, the workflow comprises four integrated steps: assessing an existing algorithm’s suitability for the target health status; developing a new algorithm using recommended methods; validating the algorithm using prescribed performance measures; and evaluating the impact of the algorithm on study results. Additionally, 13 good practice recommendations were formulated with detailed explanations. Furthermore, a practical study on sepsis identification was included to demonstrate the application of this guidance.Conclusions:The establishment of guidance is intended to aid researchers and clinicians in the appropriate and accurate development and application of algorithms for identifying health status from RCD. This guidance has the potential to enhance the credibility of findings from observational studies involving RCD.Keywords：Routinely collected healthcare data (RCD);Algorithms;Health status;Guidance26|0|0Updated：2025-12-13
METHODOLOGY
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Heart-brain axis: low blood pressure during off-pump CABG surgery is associated with postoperative heart failure AI Introduction
“In the field of xxx, expert xx has made significant research progress. They established the xx system/explored the xx topic/verified the xx conjecture, offering solutions to address xx problems and opening up new avenues for research in the field.”
Keywords：Off-pump coronary artery bypass grafting (CABG);Heart failure (HF);Individualized arterial blood pressure (ABP) management;Cerebral autoregulation (CA);Optimal ABP19|0|0Updated：2025-12-13 - “In the field of xxx, expert xx has made significant progress. They established the xx system/explored the xx topic/verified the xx conjecture, offering solutions to tackle xx problems and paving the way for future research in xx.”
Keywords：Cas9 nickase;CRISPR-Cas12a;Polymerase;Single base mutations17|0|0Updated：2025-12-13
LETTER TO THE EDITOR
- “In the field of xxx, expert xx has made significant research progress. By establishing the xx system/exploring the xx topic/verifying the xx conjecture, xx has provided solutions to solve xx problems/open up a new direction for xx research/lay a foundation for the construction of the xx system.”Keywords：Pannexin 1 (PANX1);Chronic pain;Neuropathic pain;Inflammation;animal model;Translation19|0|0Updated：2025-12-13
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Mitochondrial complex I: the key to sustained microglia activation and neuroinflammation maintenance AI Introduction
“In the field of xxx, expert xx has made significant research progress. By establishing the xx system/exploring the xx topic/verifying the xx conjecture, xx has provided solutions to solve xx problems/open up a new direction for xx research/lay a foundation for the construction of the xx system.”Keywords：Mitochondrial complex I;Neuroinflammation;Multiple sclerosis;Reverse electron transport;Microglial activation22|0|0Updated：2025-12-13
COMMENTARY
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