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Volume 12 ， Issue 1 ， 2025
- “In the field of Gulf War Illness (GWI) research, experts have explored the complex relationship between GWI symptoms, cytokine presence, and immune cell populations, providing solutions to improve diagnosis and target treatment of GWI more effectively.”
Abstract：Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction, skin rashes, musculoskeletal discomfort, and fatigue. This symptom cluster is now referred to as Gulf War Illness (GWI). As the underlying mechanisms of GWI have yet to be fully elucidated, diagnosis and treatment are based on symptomatic presentation. One confounding factor tied to the illness is the high presence of post-traumatic stress disorder (PTSD). Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction. As such, this research endeavor aimed to provide insight into the complex relationship between GWI symptoms, cytokine presence, and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.Methods:Symptom measures were gathered through the Multidimensional fatigue inventory (MFI) and 36-item short form health survey (SF-36) scales and biological measures were obtained through cytokine & cytometry analysis. Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders (DSM)-5, into GWI with high probability of PTSD symptoms (GWIH) and GWI with low probability of PTSD symptoms (GWIL). Data was analyzed using analysis of variance (ANOVA) statistical analysis along with correlation graph analysis. We mapped correlations between immune cells and cytokine signaling measures, hormones and GWI symptom measures to identify patterns in regulation between the GWIH, GWIL, and healthy control groups.Results:GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both healthy control (HC) and the GWIL subgroup. Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity (ANOVA F=4.7, P=0.01) indicating its potential usage as a biomarker for general GWI from control. While the unique identification of GWI with PTSD symptoms was less clear, the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge (ANOVA F>3.75, P<0.03). Additional differences in natural killer (NK) cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.Conclusions:We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.Keywords：Gulf war illness;Post-traumatic stress disorder;Cytokine signalling;flow cytometry;Correlation networks;Complete blood count;Subtyping;Trauma;Symptom presentation37|3|0Updated：2025-02-24 -
Acellular scaffold-based approach for
in situ genetic engineering of host T-cells in solid tumor immunotherapy AI Introduction“Targeted T-cell therapy has made significant progress in treating hematological malignancies, but faces challenges in solid tumors. Experts have developed a polyethylene glycol-based 3D scaffold system, which provides an innovative in situ localized approach for programming T-cells to target solid tumors, offering a viable alternative to in vitro manipulation of T-cells.”
Abstract：Background:Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological malignancies. However, its application to solid tumors presents significant challenges due to the limited accessibility and heterogeneity. Localized delivery of tumor-specific T-cells using biomaterials has shown promise, however, procedures required for genetic modification and generation of a sufficient number of tumor-specific T-cells ex vivo remain major obstacles due to cost and time constraints.Methods:Polyethylene glycol (PEG)-based three-dimensional (3D) scaffolds were developed and conjugated with positively charged poly-L-lysine (PLL) using carbamide chemistry for efficient loading of lentiviruses (LVs) carrying tumor antigen-specific T-cell receptors (TCRs). The physical and biological properties of the scaffold were extensively characterized. Further, the scaffold loaded with OVA-TCR LVs was implanted in B16F10 cells expressing ovalbumin (B16-OVA) tumor model to evaluate the anti-tumor response and the presence of transduced T-cells.Results:Our findings demonstrate that the scaffolds do not induce any systemic inflammation upon subcutaneous implantation and effectively recruit T-cells to the site. In B16-OVA melanoma tumor-bearing mice, the scaffolds efficiently transduce host T-cells with OVA-specific TCRs. These genetically modified T-cells exhibit homing capability towards the tumor and secondary lymphoid organs, resulting in a significant reduction of tumor size and systemic increase in anti-tumor cytokines. Immune cell profiling revealed a significantly high percentage of transduced T-cells and a notable reduction in suppressor immune cells within the tumors of mice implanted with these scaffolds.Conclusions:Our scaffold-based T-cell therapy presents an innovative in situ localized approach for programming T-cells to target solid tumors. This approach offers a viable alternative to in vitro manipulation of T-cells, circumventing the need for large-scale in vitro generation and culture of tumor-specific T-cells. It offers an off-the-shelf alternative that facilitates the use of host cells instead of allogeneic cells, thereby, overcoming a major hurdle.Keywords：Polyethylene glycol diacrylate;Poly-L-lysine;Lentiviruses;T-cell therapy;B16F10-OVA melanoma25|0|0Updated：2025-02-24 -
CT whole lung radiomic nomogram: a potential biomarker for lung function evaluation and identification of COPD AI Introduction
“In the field of chronic obstructive pulmonary disease (COPD) diagnosis, a multicenter study has made significant progress. Experts constructed an intuitive nomogram based on CT whole-lung radiomic, which has shown good performance and high accuracy in identifying COPD patients.”
Abstract：Background:Computed tomography (CT) plays a great role in characterizing and quantifying changes in lung structure and function of chronic obstructive pulmonary disease (COPD). This study aimed to explore the performance of CT-based whole lung radiomic in discriminating COPD patients and non-COPD patients.Methods:This retrospective study was performed on 2785 patients who underwent pulmonary function examination in 5 hospitals and were divided into non-COPD group and COPD group. The radiomic features of the whole lung volume were extracted. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied for feature selection and radiomic signature construction. A radiomic nomogram was established by combining the radiomic score and clinical factors. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the predictive performance of the radiomic nomogram in the training, internal validation, and independent external validation cohorts.Results:Eighteen radiomic features were collected from the whole lung volume to construct a radiomic model. The area under the curve (AUC) of the radiomic model in the training, internal, and independent external validation cohorts were 0.888 [95% confidence interval (CI) 0.869–0.906], 0.874 (95%CI 0.844–0.904), and 0.846 (95%CI 0.822–0.870), respectively. All were higher than the clinical model (AUC were 0.732, 0.714, and 0.777, respectively, P<0.001). DCA demonstrated that the nomogram constructed by combining radiomic score, age, sex, height, and smoking status was superior to the clinical factor model.Conclusions:The intuitive nomogram constructed by CT-based whole-lung radiomic has shown good performance and high accuracy in identifying COPD in this multicenter study.Keywords：Chronic obstructive pulmonary disease (COPD);Computed tomography (CT);Radiomic61|2|0Updated：2025-02-24 -
Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss AI Introduction
“In the field of Alzheimer's disease research, this study elucidates distinct protein and phosphoprotein networks between dorsal and ventral hippocampal CA1 regions, highlighting the susceptibility of the vCA1 microcircuit to AD-like tau accumulation. Notably, the efficacy of ursolic acid in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for treating AD in the future.”
Abstract：Background:Episodic memory loss is a prominent clinical manifestation of Alzheimer’s disease (AD), which is closely related to tau pathology and hippocampal impairment. Due to the heterogeneity of brain neurons, the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain unclear. Therefore, further investigation is necessary.Methods:We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis, social behavioural tests, hippocampal electrophysiology, immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and iGABASnFR. Additionally, we utilized optogenetics and administered ursolic acid (UA) via oral gavage to examine the effects of these agents on social memory in mice.Results:The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1 (vCA1) under both physiological conditions and AD-like tau pathology. As tau progressively accumulated, vCA1, especially its excitatory and parvalbumin (PV) neurons, were fully filled with mislocated and phosphorylated tau (p-Tau). This finding was not observed for dorsal hippocampal CA1 (dCA1). The overexpression of human tau (hTau) in excitatory and PV neurons mimicked AD-like tau accumulation, significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within vCA1. Photoactivating excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social memory. Notably, 1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB (TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social memory.Conclusion:This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau accumulation. Notably, our novel findings regarding the efficacy of UA in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for treating AD in the future.Keywords：Alzheimer’s disease;Tau protein;Ventral hippocampus;Social memory;Ursolic acid;Transcription factor EB (TFEB)16|0|0Updated：2025-02-24
RESEARCH
- “In the face of the global public health threat of antimicrobial resistance, the World Health Organization (WHO) has released a priority list of pathogens for which new antibiotics need to be developed. However, the discovery and introduction of new antibiotics are time-consuming and expensive. In this context, artificial intelligence (AI) has been rapidly applied to drug development, significantly improving the efficiency of discovering new antibiotics. This paper summarizes the recent progress in the field of antibacterial drug development and utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well as resistance mechanism prediction and antibiotic stewardship.”
Abstract：Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed. The discovery and introduction of novel antibiotics are time-consuming and expensive. According to WHO’s report of antibacterial agents in clinical development, only 18 novel antibiotics have been approved since 2014. Therefore, novel antibiotics are critically needed. Artificial intelligence (AI) has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel antibiotics. Here, we first summarized recently marketed novel antibiotics, and antibiotic candidates in clinical development. In addition, we systematically reviewed the involvement of AI in antibacterial drug development and utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well as resistance mechanism prediction, and antibiotic stewardship.Keywords：antibiotic;Artificial intelligence (AI);Clinical development;Machine learning (ML);Antimicrobial peptide;Phage therapy;Antibiotic stewardship25|0|0Updated：2025-02-24 -
Biomaterial-based mechanical regulation facilitates scarless wound healing with functional skin appendage regeneration AI Introduction
“In the field of skin repair and regeneration, researchers have made significant progress. They have verified the potential of targeted modulation of mechanical cues to enhance skin regeneration, promoting scarless repair and restoring multiple skin appendage functions. This provides a new direction for research in skin repair and regeneration.”
Abstract：Scar formation resulting from burns or severe trauma can significantly compromise the structural integrity of skin and lead to permanent loss of skin appendages, ultimately impairing its normal physiological function. Accumulating evidence underscores the potential of targeted modulation of mechanical cues to enhance skin regeneration, promoting scarless repair by influencing the extracellular microenvironment and driving the phenotypic transitions. The field of skin repair and skin appendage regeneration has witnessed remarkable advancements in the utilization of biomaterials with distinct physical properties. However, a comprehensive understanding of the underlying mechanisms remains somewhat elusive, limiting the broader application of these innovations. In this review, we present two promising biomaterial-based mechanical approaches aimed at bolstering the regenerative capacity of compromised skin. The first approach involves leveraging biomaterials with specific biophysical properties to create an optimal scarless environment that supports cellular activities essential for regeneration. The second approach centers on harnessing mechanical forces exerted by biomaterials to enhance cellular plasticity, facilitating efficient cellular reprogramming and, consequently, promoting the regeneration of skin appendages. In summary, the manipulation of mechanical cues using biomaterial-based strategies holds significant promise as a supplementary approach for achieving scarless wound healing, coupled with the restoration of multiple skin appendage functions.Keywords：Scarless;Wound healing;biomaterials;Mechanical cues;Skin appendages20|1|0Updated：2025-02-24 -
Immune cells: potential carriers or agents for drug delivery to the central nervous system AI Introduction
“In the field of drug delivery systems, researchers have made significant progress. They have outlined the three major brain barriers in the CNS and reviewed biomimetic strategies utilizing immune cell-based nanoparticles for drug delivery to the CNS, laying a foundation for the construction of drug delivery systems.”
Abstract：Drug delivery systems (DDS) have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery. However, the access of nanoparticles/drugs to the central nervous system (CNS) remains a challenge mainly due to the obstruction from brain barriers. Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery. Herein, we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier. We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS, as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases. Finally, we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.Keywords：Drug delivery systems;Immune cells;Blood–brain barrier;central nervous system20|0|0Updated：2025-02-24
REVIEW
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Monitoring of urinary iodine concentration in naval pilots: should iodine be supplemented or limited at coastal stations? AI Introduction
“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 address xx problems and laying the groundwork for the construction of the xx system.”Keywords：Naval pilot;Thyroid;Urinary iodine16|0|0Updated：2025-02-24
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