In recent years， with the extensive application of traditional Chinese medicine （TCM） both domestically and internationally， safety concerns associated with TCM have been frequently reported. Notably， some TCM substances traditionally regarded as ''non-toxic'' have exhibited significant adverse reactions during clinical use， drawing substantial attention to TCM safety. This study first analyzed the risk factors contributing to the potential toxicity of TCM from perspectives such as drug properties， individual constitution， and clinical medication practices. Subsequently， it proposed research strategies and methodologies for investigating potential TCM toxicity： ① conduct studies under the guidance of TCM theory， adhering to the principle of diversity and unity. ② adopt an integrated research paradigm of ''originating from clinical practice-syndrome-based foundation-returning to clinical practice-serving supervision''. ③ implement a three-tier technical system of ''Mathematical modeling-high-throughput screening via liquid chromatography-mass spectrometry （LC-MS）-systems biology'' to systematically elucidate the causes， material basis， and mechanisms of toxicity. Finally， scientific regulatory recommendations for potential TCM toxicity are proposed： ① establish a multidimensional prevention and control system addressing drug properties， physical constitution factors， and clinical medication practices. ② address the impact of modern processing techniques on the safety of new TCM drugs. ③ strengthen the revision of standards for Chinese medicinal materials to ensure their safety. ④ account for disease-syndrome combination animal models and interspecies differences in safety assessment outcomes. This study aims to overcome critical challenges in TCM regulation by advancing evaluation through research and driving research through evaluation. By establishing a high-level scientific regulatory framework， it seeks to not only safeguard clinical medication safety but also propel the high-quality development of the TCM industry， thereby providing scientific support for the inheritance and innovative evolution of TCM.

In recent years， with the extensive application of traditional Chinese medicine （TCM） both domestically and internationally， safety concerns associated with TCM have been frequently reported. Notably， some TCM substances traditionally regarded as ''non-toxic'' have exhibited significant adverse reactions during clinical use， drawing substantial attention to TCM safety. This study first analyzed the risk factors contributing to the potential toxicity of TCM from perspectives such as drug properties， individual constitution， and clinical medication practices. Subsequently， it proposed research strategies and methodologies for investigating potential TCM toxicity： ① conduct studies under the guidance of TCM theory， adhering to the principle of diversity and unity. ② adopt an integrated research paradigm of ''originating from clinical practice-syndrome-based foundation-returning to clinical practice-serving supervision''. ③ implement a three-tier technical system of ''Mathematical modeling-high-throughput screening via liquid chromatography-mass spectrometry （LC-MS）-systems biology'' to systematically elucidate the causes， material basis， and mechanisms of toxicity. Finally， scientific regulatory recommendations for potential TCM toxicity are proposed： ① establish a multidimensional prevention and control system addressing drug properties， physical constitution factors， and clinical medication practices. ② address the impact of modern processing techniques on the safety of new TCM drugs. ③ strengthen the revision of standards for Chinese medicinal materials to ensure their safety. ④ account for disease-syndrome combination animal models and interspecies differences in safety assessment outcomes. This study aims to overcome critical challenges in TCM regulation by advancing evaluation through research and driving research through evaluation. By establishing a high-level scientific regulatory framework， it seeks to not only safeguard clinical medication safety but also propel the high-quality development of the TCM industry， thereby providing scientific support for the inheritance and innovative evolution of TCM.

Narrative medicine focuses on empathy， relevance， and emotion， precisely aligning with the elements of “clown doctor” such as compassion， interaction， and pain relief. From the perspective of narrative medicine， the practice of “clown doctors” not only focuses on the emotional changes of patients but also enhances their sense of belonging by recreating their experiences. The key element for the success of “clown doctors” lies in establishing a multi-dimensional trust relationship among medical workers， patients， colleagues， and society， while ensuring their practice adheres to medical ethics norms. “Clown doctors” should concentrate on dimensions such as concept dissemination， clinical application， social recognition， and ethical practice of narrative medicine. They should also constantly optimize narrative techniques， deepen the understanding of patients’ stories， and intervene in the medical process in a more delicate and comprehensive way， thereby fostering in-depth communication and understanding between doctors and patients.

Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), and hydrogen (H₂), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H₂S significantly accelerates endothelial cell migration for neovascularization, and H₂ acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.

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.

Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), and hydrogen (H₂), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H₂S significantly accelerates endothelial cell migration for neovascularization, and H₂ acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.

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.

BACKGROUND:Streptococcus mutans is an important pathogen of dental caries,and timely detection of its levels is of great significance for early detection and treatment of dental caries. OBJECTIVE:To evaluate the effect of loop-mediated isothermal amplification(FTA-LAMP)direct extraction of Streptococcus mutans DNA. METHODS:(1)Bacterial suspensions containing ATCC standard strains(Streptococcus mutans)were prepared and inoculated into the brain-heart leachate medium.After mixed thoroughly,the mixture was then diluted in a 10-fold gradient into seven concentrations(4.2×107,4.2×106,4.2×105,4.2×104,4.2×103,4.2×102,4.2×10 CFU/mL),two parallel controls were made for each dilution level,and sterile water was used as a blank control.(2)The DNA of Streptococcus mutans was extracted using FTA Elute card,boiling method,kit extraction and lysate extraction methods separately and then amplified using LAMP technology was amplified.A specificity test was also performed to compare the differences between the four DNA extraction methods.RESULTS AND CONCLUSION:The DNA extracted by all four methods met the requirements for LAMP amplification.Specificity test results showed that only Streptococcus mutans could specifically amplify the target gene.The detection limit value of the DNA concentration was 4.2×103 CFU/mL for the lysate method,4.2×104 CFU/mL for the FTA Elute card extraction method,4.2×106 CFU/mL for the kit extraction method,and 4.2×107 CFU/mL for the boiling method.In the other aspects of the four extraction methods,the kit extraction method had the highest experimental cost,number of steps and time;the other three methods had the same number of steps,with the FTA Elute card method requiring the least amount of instruments,the boiling method having the lowest single cost,and the lysate extraction method taking the least amount of time.Only a small amount of bacteria were needed for successful extraction using both the FTA Elute card and lysate extraction methods.Compared with the FTA Elute card method,the lysate extraction method was superior in terms of time,but it had a high single cost and required more equipment.To conclude,the FTA-LAMP technology established in this study has the advantages of ease of operation,high specificity,high sensitivity,and visualization,which is expected to be a new way for efficient extraction and detection of Streptococcus mutans.

ObjectiveWe reviewed the existing experimental studies about renal injury-inducing Chinese medicine and systematically analyzed the toxicity mechanisms， toxic components， toxicity attenuation measures， and modern evaluation methods of renal injury-inducing Chinese medicine. The results are expected to provide new ideas for the modern research on kidney injury-inducing Chinese medicine， offer new breakthrough points for the toxicity attenuation of Chinese medicine by compatibility and processing， and give insights into the future research of Chinese medicine toxicology on the basis of ensuring the safety and scientific application of Chinese medicine. MethodsThe animal， cell， and clinical studies of kidney injury-inducing Chinese medicine were retrieved from CNKI， Wanfang Data， VIP， PubMed， and Web of Science. The names and toxic components of renal injury-inducing Chinese medicine， renal injury sites， toxicity mechanisms， toxicity attenuation measures， and related evaluation methods were summarized. ResultsThe toxicity mechanisms of kidney injury-inducing Chinese medicine mainly involved oxidative stress， endoplasmic reticulum stress， inflammatory cell infiltration， and organic anion transporters. Processing and compatibility were the main toxicity attenuation measures. The evaluation methods encompassed animal experiments， cell models， network pharmacology， metabolomics， toxicology genomics， and fluorescent probe technology. ConclusionAt present， the toxicological verification of kidney injury-inducing Chinese medicine starts from toxic components and combines various experimental methods， which is more comprehensive and systematic than the previous studies based on only animal experiments. According to the classical theories of traditional Chinese medicine， the toxicity of kidney injury-inducing Chinese medicine is mainly attenuated by decocting in water， steaming， and frying. With the progress of science and technology， new processing methods for toxicity attenuation are emerging， and structural transformation， fermentation， and microwave methods are the key research directions of toxicity attenuation of Chinese medicine in recent years.

ObjectiveWe reviewed the existing experimental studies about renal injury-inducing Chinese medicine and systematically analyzed the toxicity mechanisms， toxic components， toxicity attenuation measures， and modern evaluation methods of renal injury-inducing Chinese medicine. The results are expected to provide new ideas for the modern research on kidney injury-inducing Chinese medicine， offer new breakthrough points for the toxicity attenuation of Chinese medicine by compatibility and processing， and give insights into the future research of Chinese medicine toxicology on the basis of ensuring the safety and scientific application of Chinese medicine. MethodsThe animal， cell， and clinical studies of kidney injury-inducing Chinese medicine were retrieved from CNKI， Wanfang Data， VIP， PubMed， and Web of Science. The names and toxic components of renal injury-inducing Chinese medicine， renal injury sites， toxicity mechanisms， toxicity attenuation measures， and related evaluation methods were summarized. ResultsThe toxicity mechanisms of kidney injury-inducing Chinese medicine mainly involved oxidative stress， endoplasmic reticulum stress， inflammatory cell infiltration， and organic anion transporters. Processing and compatibility were the main toxicity attenuation measures. The evaluation methods encompassed animal experiments， cell models， network pharmacology， metabolomics， toxicology genomics， and fluorescent probe technology. ConclusionAt present， the toxicological verification of kidney injury-inducing Chinese medicine starts from toxic components and combines various experimental methods， which is more comprehensive and systematic than the previous studies based on only animal experiments. According to the classical theories of traditional Chinese medicine， the toxicity of kidney injury-inducing Chinese medicine is mainly attenuated by decocting in water， steaming， and frying. With the progress of science and technology， new processing methods for toxicity attenuation are emerging， and structural transformation， fermentation， and microwave methods are the key research directions of toxicity attenuation of Chinese medicine in recent years.