Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.

BackgroundPatients with colorectal cancer are frequently comorbid with depression， which severely affects the quality of life and treatment compliance， while compromising the efficacy of anticancer treament and prognosis. Current therapeutic strategies still have notable limitations， particularly the lack of systematic and targeted synergistic regimens that integrate oncological management and anti-depressive intervention. It is of great clinical significance to explore a safe and effective new comprehensive intervention protocol and clarify its underlying mechanism of action. ObjectiveTo explore the effectiveness and safety of Shugan Yunpi Decoction in alleviating depressive and anxiety symptoms in colorectal cancer patients with depressive disorder through the PI3K-AKT signaling pathway， in order to provide references for the comprehensive treatment of colorectal cancer and depressive disorder. MethodsThis study was a randomized controlled trial. A total of 106 patients admitted to the Baoding No.1 Hospital of traditional Chinese medicine from November 2023 to July 2025 were enrolled， who met the diagnostic criteria for the Chinese protocol of diagnosis and treatment of colorectal cancer （2023 edition） and the diagnostic criteria for depressive disorder as specified in the Chinese Classification and Diagnostic Criteria of Mental Disease， third edition （CCMD-3）. Patients were divided into the study group and the control group using a random number table， with 53 cases in each group. The control group received conventional chemotherapy combined with traditional Chinese medicine five-element music therapy， while the study group received conventional chemotherapy combined with Shugan Yunpi Decoction therapy. Both groups were treated for 8 weeks. Depressive and anxiety symptoms were assessed using the Hamilton Depression Scale-17 item（HAMD-17） and Hamilton Anxiety Scale （HAMA）， respectively. Western blot protein immunoblotting was used to detect the expression levels of PI3K， AKT， and pAKT. Real-time fluorescence quantitative reverse transcription polymerase chain reaction （qRT-PCR） was used to detect the expression levels of PI3K mRNA and AKT mRNA. Adverse reactions were recorded using a self-designed adverse reaction record form. ResultsRepeated measures analysis of variance showed that the time effects （F=139.336， 234.747）， group effects （F=43.900， 101.266）， and time-group interaction effects （F=13.409， 43.216） for HAMD-17 and HAMA scores in both groups were statistically significant （P<0.01）. After 4 and 8 weeks of treatment， the HAMD-17 and HAMA scores in both groups were lower than those before treatment， with statistically significant differences （P<0.05）. HAMD-17 and HAMA scores in the study group were lower than those in the control group （P<0.05）. The time effects （F=571.356， 309.266， 414.492）， group effects （F=6.901， 26.361， 39.362）， and time-group interaction effects （F=18.592， 19.266， 33.484） for the protein expression levels of PI3K， AKT， and pAKT in both groups were all statistically significant （P<0.01）. After 8 weeks of treatment， the protein expression levels of PI3K and pAKT in the study group were lower than those in the control group， while the AKT protein expression level was higher than that in the control group（P<0.01）. The time effects （F=338.555， 225.059）， group effects （F=5.429， 9.726）， and time-group interaction effects （F=12.953， 21.214） for PI3K mRNA and AKT mRNA expression levels in two groups were all statistically significant （P<0.01）. After 8 weeks of treatment， the expression levels of PI3K mRNA and AKT mRNA in the study group were lower than those in the control group （P<0.05）. The incidence of adverse reactions in the study group was lower than that in the control group （χ²=4.810， P<0.05）. ConclusionShugan Yunpi Decoction may help to ameliorate depressive and anxiety symptoms in colorectal cancer patients with depressive disorder by regulating the PI3K-AKT signaling pathway， decreasing the levels of PI3K， pAKT， PI3K mRNA， and AKT mRNA， with a favorable safety profile. ［Funded by Baoding City Science and Technology Planning Project （number， 2341ZF291）］

Objective Magnetoreception, the remarkable ability of diverse animals to sense and utilize the geomagnetic field for orientation and navigation, remains a molecularly unresolved mystery in sensory biology. The putative magnetoreceptor (MagR, previously known as IscA1) is a highly conserved iron-sulfur protein implicated in both magnetoreception and iron metabolism; however, the functional diversity among its cross-species homologs remains poorly understood. Cellular morphology is a key genetically determined trait that can be altered through genetic or environmental modifications—a process known as cell morphology engineering. Constructing engineered cells with specific morphological features and magnetic sensitivity to achieve remote, non-invasive magnetic modulation represents a crucial goal in this field with significant application potential. Therefore, this study aims to systematically investigate the effects of MagR heterologous expression on bacterial morphology and magnetic sensing capabilities, screen for MagR-based magnetically sensitive morphology engineering pathways, and reveal the underlying molecular mechanisms. Methods We systematically screened 28 MagR homologous genes from diverse prokaryotic and animal taxa to evaluate their expression and corresponding phenotypic effects in Escherichia coli (E. coli). To compare the differential magnetic responses among bacteria expressing various recombinant MagR proteins, we utilized high-throughput automated bright-field microscopic imaging and scanning electron microscopy (SEM). Furthermore, comprehensive biochemical and biophysical characterizations of iron and iron-sulfur cluster binding were performed using Ferrozine colorimetric assays, electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) absorption, and circular dichroism (CD) spectroscopy. Additionally, 100 mT static magnetic field (SMF) exposure experiments were conducted to assess magnetically tunable phenotypes, while the intrinsic magnetic properties of purified MagR proteins were directly measured using a superconducting quantum interference device (SQUID) magnetometer. Results Our results demonstrated that the heterologous expression of MagR homologs induced varying degrees of bacterial filamentation. From this comprehensive screen, two distinct morphological patterns were identified: hydra (Hydra vulgaris) MagR (hyMagR) promoted uniform cell elongation and filamentation, exhibiting robust magnetic sensitivity manifested as significantly enhanced filamentation under the 100 mT SMF. In contrast, pigeon (Columba livia) MagR (clMagR) induced only low-frequency, extreme filamentation (sporadically exceeding 80 μm) with a relatively weaker magnetic morphological response. Mechanistically, our data unambiguously proved that these phenotypic differences are primarily driven by distinct iron redox preferences rather than total cellular iron accumulation. Specifically, hyMagR preferentially binds ferrous iron (Fe²⁺), whereas clMagR favors ferric iron (Fe³⁺) and forms more stable iron-sulfur clusters. Intriguingly, although SQUID magnetometry showed that purified clMagR exhibited approximately five-fold higher mass magnetic susceptibility than hyMagR, its cellular magnetic response was weaker. We hypothesize that the Fe²⁺-preferred intracellular environment associated with hyMagR overexpression primes the cell for enhanced generation of reactive oxygen species (ROS) via the Fenton reaction. Exposure to an SMF synergizes with this primed redox state, triggering the bacterial SOS response and upregulating cell division inhibitors to efficiently induce uniform filamentation. Conclusion Our findings identify the Fe²⁺/Fe³⁺ redox state as a critical determinant of MagR-mediated morphological remodeling and magnetic responsiveness. This discovery suggests a potential strategy for engineering magnetically responsive cellular systems for synthetic biology applications, and provides a plausible framework, which potentially combines intrinsic protein magnetism with redox-state modulation, for further investigating the evolutionary mechanisms of MagR-mediated magnetoreception.

Objective Magnetoreception, the remarkable ability of diverse animals to sense and utilize the geomagnetic field for orientation and navigation, remains a molecularly unresolved mystery in sensory biology. The putative magnetoreceptor (MagR, previously known as IscA1) is a highly conserved iron-sulfur protein implicated in both magnetoreception and iron metabolism; however, the functional diversity among its cross-species homologs remains poorly understood. Cellular morphology is a key genetically determined trait that can be altered through genetic or environmental modifications—a process known as cell morphology engineering. Constructing engineered cells with specific morphological features and magnetic sensitivity to achieve remote, non-invasive magnetic modulation represents a crucial goal in this field with significant application potential. Therefore, this study aims to systematically investigate the effects of MagR heterologous expression on bacterial morphology and magnetic sensing capabilities, screen for MagR-based magnetically sensitive morphology engineering pathways, and reveal the underlying molecular mechanisms. Methods We systematically screened 28 MagR homologous genes from diverse prokaryotic and animal taxa to evaluate their expression and corresponding phenotypic effects in Escherichia coli (E. coli). To compare the differential magnetic responses among bacteria expressing various recombinant MagR proteins, we utilized high-throughput automated bright-field microscopic imaging and scanning electron microscopy (SEM). Furthermore, comprehensive biochemical and biophysical characterizations of iron and iron-sulfur cluster binding were performed using Ferrozine colorimetric assays, electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) absorption, and circular dichroism (CD) spectroscopy. Additionally, 100 mT static magnetic field (SMF) exposure experiments were conducted to assess magnetically tunable phenotypes, while the intrinsic magnetic properties of purified MagR proteins were directly measured using a superconducting quantum interference device (SQUID) magnetometer. Results Our results demonstrated that the heterologous expression of MagR homologs induced varying degrees of bacterial filamentation. From this comprehensive screen, two distinct morphological patterns were identified: hydra (Hydra vulgaris) MagR (hyMagR) promoted uniform cell elongation and filamentation, exhibiting robust magnetic sensitivity manifested as significantly enhanced filamentation under the 100 mT SMF. In contrast, pigeon (Columba livia) MagR (clMagR) induced only low-frequency, extreme filamentation (sporadically exceeding 80 μm) with a relatively weaker magnetic morphological response. Mechanistically, our data unambiguously proved that these phenotypic differences are primarily driven by distinct iron redox preferences rather than total cellular iron accumulation. Specifically, hyMagR preferentially binds ferrous iron (Fe²⁺), whereas clMagR favors ferric iron (Fe³⁺) and forms more stable iron-sulfur clusters. Intriguingly, although SQUID magnetometry showed that purified clMagR exhibited approximately five-fold higher mass magnetic susceptibility than hyMagR, its cellular magnetic response was weaker. We hypothesize that the Fe²⁺-preferred intracellular environment associated with hyMagR overexpression primes the cell for enhanced generation of reactive oxygen species (ROS) via the Fenton reaction. Exposure to an SMF synergizes with this primed redox state, triggering the bacterial SOS response and upregulating cell division inhibitors to efficiently induce uniform filamentation. Conclusion Our findings identify the Fe²⁺/Fe³⁺ redox state as a critical determinant of MagR-mediated morphological remodeling and magnetic responsiveness. This discovery suggests a potential strategy for engineering magnetically responsive cellular systems for synthetic biology applications, and provides a plausible framework, which potentially combines intrinsic protein magnetism with redox-state modulation, for further investigating the evolutionary mechanisms of MagR-mediated magnetoreception.

The development of traditional Chinese medicine (TCM) diagnosis and treatment has undergone multiple paradigms, evolving from sporadic experiential practices to systematic approaches in syndrome differentiation and treatment and further integration of disease and syndrome frameworks. TCM is a vital component of the medical system, valued alongside Western medicine. Treatment based on syndrome differentiation embodies both personalized treatment and holistic approaches; however, the inconsistency and lack of stability in syndrome differentiation limit clinical efficacy. The existing integration of diseases and syndromes primarily relies on patchwork and embedded systems, where the full advantages of synergy between Chinese and Western medicine are not fully realized. Recently, driven by the development of diagnosis and treatment concepts and advances in analytical technology, Western medicine has been rapidly transforming from a traditional biological model to a precision medicine model. TCM faces a similar need to progress beyond traditional syndrome differentiation and disease-syndrome integration toward a more precise diagnosis and treatment paradigm. Unlike the micro-level precision trend of Western medicine, precision diagnosis and treatment in TCM is primarily reflected in data-driven applications that incorporate information at various levels, including precise syndrome differentiation, medication, disease management, and efficacy evaluation. The current priority is to accelerate the development of TCM precision diagnosis and treatment technology platforms and advance discipline construction in this area.

OBJECTIVE To explore the isolation rates,drug resistance and molecular epidemiological characteristics of carbapenem-resistant gram-negative bacilli(CRGNB)isolated from intensive care units(ICU)of a tertiary hos-pital so as to provide bases for prevention and control of the nosocomial infections caused by CRGNB.METHODS The environmental surfaces that were high frequently contacted by the patients with CRGNB infections[carbapen-em-resistant Klebsiella pneumoniae(CRKP),carbapenem-resistant Acinetobacter baumannii(CRAB),carbap-enem-resistant Pseudomonas aeruginosa(CRPA)]and their hands were randomly sampled from the ICU of a ter-tiary three-A hospital from Apr.2024 to Aug.2024.Multilocus sequence typing(MLST)and detection of drug re-sistance genes were performed by means of complete genome sequencing technique and bioinformatics,and the ho-mology between the CRGNB strains isolated from the patients and the strains isolated from their surrounding was observed.RESULTS Totally 30(7.85％)strains of CRGNB were isolated,23(6.02％)of which were CRKP,7(1.83％)were CRAB,and no strain of CRPA was detected.The molecular subtyping showed that ST 11(93.33％)was dominant among the CRKP strains,and ST2(69.23％)was dominant among the CRAB strains.The phylogenetic analysis indicated that there were clonal transmission tendencies of CRKP-ST11 and CRAB-ST2.The analysis of drug resistance genes showed that the CRAB strains mainly carried ant(3")-lla(100％),blaOXA-23(92.31％)and amvA(92.31％);blaOXA-23 and blaOXA-66 were the major carbapenems resistance genes;the CRKP strains mainly carried the drug resistance genes emrDh,rmtB1,fosA and kdeA(all were 96.67％),followed by the carbapenems resistance gene blaKPC-2(90.00％).CONCLUSIONS ST11 is the predomi-nant molecular subtype for CRGNB among the CRKP strains isolated from the ICU,anf ST2 predominant among the CRAB strains;the carrying rates of drug resistance genes are high.There is risk of clonal transmission.It is necessary to strengthen the monitoring and take comprehensive infection control measures so as to reduce the incidence of nosocomial infections.

Ergopeptines or their derivatives are widely used for treating neurodegenerative and cerebrovascular diseases. The nonribosomal peptide synthetase-d-lysergyl peptide synthetase A (LPSA) determines ergopeptine formation but the detailed mechanism remains to be elucidated. Here, we characterized two LPSAs from Claviceps purpurea Cp-1 strain through heterologous expression in Aspergillus nidulans feeding with d-lysergic acid. We proved that Cp-LPSA1 catalyzed the formation of ergocornine, α-ergocryptine, and β-ergocryptine, precisely controlled by the substrate specificity of its three modules. Cp-LPSA2 was initially inactive but could be restored to catalyze α-ergosine formation. Using this platform, we validated that P1-LPSA1 and P1-LPSA2 from the reported C. purpurea P1 strain catalyzed ergotamine and α-ergocryptine formation, respectively. Typically, the non-ribosomal peptide codes implicated in every module of the LPSAs were defined and elucidated, in which certain key residues could play a switched role for substrate specificity and product interconversion. By constructing chimeric LPSAs through module assembly, the production of the desired ergopeptines was achieved. Notably, 1.46 mg/L of α-ergocryptine and 1.09 mg/L of ergotamine were produced respectively by mixed-culture of C. paspali No. 24 (fermentation supernatant) and the recombinants of A. nidulans. Our findings provide insights into the biosynthetic mechanism of ergopeptines and lay a foundation for directed ergopeptine biosynthesis.

OBJECTIVE: Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA. METHODS: Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment. RESULTS: Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex. CONCLUSION EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals ; Electroacupuncture ; Male ; Magnetic Resonance Imaging ; Depression/diagnostic imaging* ; Mice, Inbred C57BL ; Brain/diagnostic imaging* ; Disease Models, Animal ; Mice ; Pain/diagnostic imaging* ; Acupuncture Points

The classic formula Fangji Fulingtang is from ZHANG Zhongjing's Synopsis of the Golden Chamber in the Eastern Han dynasty. It is composed of Stephaniae Tetrandrae Radix， Astragali Radix， Cinnamomi Ramulus， Poria， and Glycyrrhizae Radix et Rhizoma， with the effects of reinforcing Qi and invigorating spleen， warming Yang and promoting urination. By a review of ancient medical books， this paper summarizes the composition， original plants， processing， dosage， decocting methods， indications and other key information of Fangji Fulingtang， aiming to provide a literature basis for the research， development， and clinical application of preparations based on this formula. Synonyms of Fangji Fulingtang exist in ancient medical books， while the formula composition in the Synopsis of the Golden Chamber is more widespread and far-reaching. In this formula， Stephaniae Tetrandrae Radix， Astragali Radix， Cinnamomi Ramulus， Poria， and Glycyrrhizae Radix et Rhizoma are the dried root of Stephania tetrandra， the dried root of Astragalus embranaceus var. mongholicus， the dried shoot of Cinnamomum cassia， the dried sclerotium of Poria cocos， and the dried root and rhizome of Glycyrrhiza uralensis， respectively. Fangji Fulingtang is mainly produced into powder， with the dosage and decocting method used in the past dynasties basically following the original formula. Each bag is composed of Stephaniae Tetrandrae Radix 13.80 g， Astragali Radix 13.80 g， Cinnamomi Ramulus 13.80 g， Poria 27.60 g， and Glycyrrhizae Radix et Rhizoma 9.20 g. The raw materials are purified， decocted in water from 1 200 mL to 400 mL， and the decoction should be taken warm， 3 times a day. Fangji Fulingtang was originally designed for treating skin edema， and then it was used to treat impediment in the Qing dynasty. In modern times， it is mostly used to treat musculoskeletal and connective tissue diseases and circulatory system diseases， demonstrating definite effects on various types of edema and heart failure. This paper clarifies the inheritance of Fangji Fulingtang and reveals its key information （attached to the end of this paper）， aiming to provide a theoretical basis for the development of preparations based on this formula.