Objective To determine the molecular mechanism of Yuchang granule (YCG) against ulcerative colitis （UC） by network pharmacology-based approach combined with molecular docking. Methods TCMSP and HIT database were utilized to search the active components and potential targets of YCG. The effective targets of UC were obtained by GeneCards, CTD, and DisGeNET databases. Venn Diagram was exploited to receive common targets of YCG and UC. Network maps of the TCM of YCG-active component-common targets were constructed by the Cytoscape software to gain key active components. Protein-protein interaction （PPI） of common targets was constructed by the STRING database obtaining core common targets. The mechanism and therapeutic effects of YCG on UC were explored via gene ontology （GO） and the biological pathway （KEGG） enrichment analyses. Molecular docking technology was carried out to verify the combination of core active components with key common targets. Results 98 active components and 237 potential targets were sieved from YCG, and 1061 effective targets were screened from UC. 94 common targets of YCG and UC were regarded as potential therapeutic targets. Bioinformatics analysis revealed that quercetin, luteolin, β-quebrachol, stigmasterol, and kaempferol may be the potential candidate agents. Tumor necrosis factor （TNF）, serine/threonine-protein kinase （AKT1）, tumor protein p53 （TP53）, interleukin-6 （IL-6） and IL-1β could become potential therapeutic targets. KEGG showed pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and IL-17 signaling pathway might play an important role in YCG against UC. Molecular docking results showed that quercetin combined well with TNF, AKT1, and TP53. And stigmasterol did well with AKT1. Conclusion This study comprehensively illustrated the potential candidate agents, potential therapeutic targets, and pathways of YCG against UC. It also illustrated that YCG could act on multiple targets through multi-pathway treating UC.

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.

AIM:To investigate the role of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)in hypoxia-induced autophagy and apopto-sis in endothelial cells.METHODS:Human umbili-cal vein endothelial cells(HUVECs)were exposed to hypoxia(1％O2)for varying durations(0,6,12,24 h)to evaluate autophagy and apoptosis levels.LOX-1 was further intervened to explore its effects on autophagy and apoptosis.GFP-LC3B adenovirus in-fection was observed under fluorescence microsco-py to assess LC3B expression.Autophagosomes were detected by transmission electron microscopy(TEM).LOX-1 mRNA levels were measured using re-al-time PCR.Protein expression of LOX-1,LC3Ⅱ/Ⅰ,Beclin-1,Atg5,cleaved-caspase 3,Bax,and Bcl-2 was analyzed by Western blot.Reactive oxygen spe-cies(ROS)levels were quantified using the DCFH-DA fluorescent probe.Apoptosis was assessed via Hoechst staining and flow cytometry(Annexin V-PI double staining).RESULTS:Hypoxia(1％O2,24 h)significantly increased LC3Ⅱ puncta under fluores-cence microscopy,upregulated LC3Ⅱ/Ⅰ protein ex-pression,and induced autophagosome formation observed by TEM.Hypoxia elevated ROS produc-tion and promoted apoptosis.LOX-1 mRNA and protein expression were upregulated in hypoxic HU-VECs.LOX-1 siRNA intervention markedly reversed hypoxia-induced autophagy,downregulating au-tophagy-related proteins(Beclin-1,Atg5,LC3Ⅱ/Ⅰ).LOX-1 siRNA also suppressed ROS generation and inhibited apoptosis,as evidenced by decreased ex-pression of cleaved-caspase 3 and Bax,and in-creased Bcl-2 levels.CONCLUSION:Hypoxia in-duced upregulation of LOX-1 expression to produce ROS,thereby promoting autophagy and apoptosis in endothelial cells.

Objective:To compare the clinical effect of deproteinized calf blood extract (DCBE) eye drops and 0.3% sodium hyaluronate eye drops in the treatment of diabetic cataract patients with dry eye after phacoemulsification.Methods:A randomized controlled study was performed.A total of 112 patients (116 eyes) with type Ⅱ diabetes combined with cataract and dry eye who underwent phacoemulsification in the Eye Hospital of Shandong First Medical University from January 2022 to September 2022 were selected.Patients were divided into DCBE group (49 cases, 51 eyes) and sodium hyaluronate group (63 cases, 65 eyes) by the random number table method.Patients received DCBE eye drops and 0.3% sodium hyaluronate eye drops after surgery according to grouping.Preoperative and postoperative 1 week, 1 month subjective symptoms of dry eye, corneal edema grade, tear film breakup time (TBUT), corneal fluorescein staining (CFS) and Schirmer Ⅰ test (SⅠt) results were recorded and compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.SDSYKYY202112-1).Written informed consent was obtained from each subject.Results:There were significant differences in dry eye symptom score, TBUT and SⅠt at different time points between before and after surgery ( Ftime=323.202, 102.771, 151.876; all P<0.001).Dry eye symptom score decreased and SⅠt increased in the two groups at 1 week and 1 month after surgery compared with before surgery, and the differences were statistically significant (all P<0.017).TBUT was longer at 1 week and 1 month after surgery compared with before surgery in the DCBE group, and TBUT at 1 month after surgery was longer than that before surgery in the sodium hyaluronate group, and the differences were statistically significant (all P<0.017).There were statistically significant differences in CFS scores between the two groups at different time points before and after surgery ( Fgroup=5.391, P=0.022; Ftime=142.402, P<0.001).The CFS scores of both groups at 1 week and 1 month after surgery were lower than those before surgery, and CFS scores in the DCBE group were lower than those in the sodium hyaluronate group, with statistically significant differences (all P<0.017).One week after surgery, the proportion of patients with corneal edema in the DCBE group was 5.9%(3/51), which was significantly lower than 20.0%(13/65) in the sodium hyaluronate group ( χ2=4.790, P=0.029). Conclusions:DCBE eye drops can promote corneal repair, stabilize tear film and improve dry eye discomfort in early postoperative period in diabetic cataract, and its overall effect is better than 0.3% sodium hyaluronate eye drops.

Objective:To compare the clinical effect of deproteinized calf blood extract (DCBE) eye drops and 0.3% sodium hyaluronate eye drops in the treatment of diabetic cataract patients with dry eye after phacoemulsification.Methods:A randomized controlled study was performed.A total of 112 patients (116 eyes) with type Ⅱ diabetes combined with cataract and dry eye who underwent phacoemulsification in the Eye Hospital of Shandong First Medical University from January 2022 to September 2022 were selected.Patients were divided into DCBE group (49 cases, 51 eyes) and sodium hyaluronate group (63 cases, 65 eyes) by the random number table method.Patients received DCBE eye drops and 0.3% sodium hyaluronate eye drops after surgery according to grouping.Preoperative and postoperative 1 week, 1 month subjective symptoms of dry eye, corneal edema grade, tear film breakup time (TBUT), corneal fluorescein staining (CFS) and Schirmer Ⅰ test (SⅠt) results were recorded and compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.SDSYKYY202112-1).Written informed consent was obtained from each subject.Results:There were significant differences in dry eye symptom score, TBUT and SⅠt at different time points between before and after surgery ( Ftime=323.202, 102.771, 151.876; all P<0.001).Dry eye symptom score decreased and SⅠt increased in the two groups at 1 week and 1 month after surgery compared with before surgery, and the differences were statistically significant (all P<0.017).TBUT was longer at 1 week and 1 month after surgery compared with before surgery in the DCBE group, and TBUT at 1 month after surgery was longer than that before surgery in the sodium hyaluronate group, and the differences were statistically significant (all P<0.017).There were statistically significant differences in CFS scores between the two groups at different time points before and after surgery ( Fgroup=5.391, P=0.022; Ftime=142.402, P<0.001).The CFS scores of both groups at 1 week and 1 month after surgery were lower than those before surgery, and CFS scores in the DCBE group were lower than those in the sodium hyaluronate group, with statistically significant differences (all P<0.017).One week after surgery, the proportion of patients with corneal edema in the DCBE group was 5.9%(3/51), which was significantly lower than 20.0%(13/65) in the sodium hyaluronate group ( χ2=4.790, P=0.029). Conclusions:DCBE eye drops can promote corneal repair, stabilize tear film and improve dry eye discomfort in early postoperative period in diabetic cataract, and its overall effect is better than 0.3% sodium hyaluronate eye drops.

Objective:To evaluate the causal relationship between IL-7 and IL-7Rα and ankylosing spondylitis(AS)using the Mendelian randomization(MR)method.Methods:This study was based on gene-wide association study(GWAS)summary data,con-structing instrumental variables(IV)using single nucleotide polymorphisms(SNPs).We respectively adopt Inverse variance weighted(IVW),MR-Egger mode and Weighted median(WM)mode to assess the causal relation between IL-7/IL-7Rα and AS.In addition,we also conducted sensitivity tests,including the heterogeneity test,the pleiotropy test,the leave-one-out approach and the MR-PRESSO test.Results:IL-7 and IL-7Rα were respectively included in 9 and 5 IVs that could be used for MR analysis.Results of IVW analysis revealed a reliable causal relationship between IL-7 and IL-7Rα and AS[IL-7:P=0.025 2,OR(95%CI)=0.999 4(0.989 1～0.999 9);IL-7Rα:P=0.008 3,OR(95%CI)=1.000 6(1.000 2～1.001 0)].Cochranes Q test(IL-7:P=0.999 7;IL-7Rα:P=0.946 9)showed that all studies had good homogeneity.The results of a leave-one-out sensitivity analysis suggested that causal associations were not strongly influenced by any selected IVs.The intercept of the MR-Egger regression further showed that pleiotropy did not bias the causal effect in this study.Conclusion:Both IL-7 and IL-7Rα have a strong causal relationship with AS,among which IL-7 is a protec-tive factor for AS,and IL-7Rα is a risk factor for AS.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective:To investigate the application value of gastric suspension method in supra-pancreatic lymph node dissection of laparoscopic radical gastrectomy of gastric cancer.Method:The retrospective cohort study was conducted. The clinicopathological data of 84 patients who under-went laparoscopic radical gastrectomy of gastric cancer at Zhejiang Cancer Hospital from August 2023 to July 2024 were collected. There were 61 males and 23 females, aged (64±11)years. Of the 84 patients, 42 patients undergoing supra-pancreatic lymph node dissection during laparoscopic radical gastrectomy of gastric cancer with traditional method for surgical field exposure were divided into the control group, and 42 patients undergoing supra-pancreatic lymph node dissection during laparoscopic radical gastrectomy of gastric cancer with gastric suspension method for surgical field exposure were divided into the suspension group. Observation indicators: (1) surgical conditions; (2) postoperative conditions. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Results:(1) Surgical condi-tions. The time for supra-pancreatic lymph node dissection of the control group was (78±14)minutes. Number of grasping operations was 116±34, number of bleeding sites caused by grasping operations was 7.8±2.7, and operation time was (3.9±0.8)hours. The above indicators of the suspension group were (59±12)minutes, 68±19, 2.1±1.5, and (3.3±0.7)hours, respectively. There were significant diffe-rences in the above indicators between the two groups ( t=5.42, 8.10, 8.31, 3.14, P<0.05). (2) Post-operative conditions. The tumor diameter was 2.5(2.0,3.5)cm for patients of the control group, versus 3.0(2.4, 4.4)cm for patients of the suspension group, showing a significant difference between the two groups ( Z=-1.98, P<0.05). Conclusion:Compared with the traditional non-suspension method, the gastric suspension method in laparoscopic radical gastrectomy of gastric cancer for supra-pancreatic lymph node dissection is associated with shorter operation time and less trauma.

Objective:To evaluate the causal relationship between IL-7 and IL-7Rα and ankylosing spondylitis(AS)using the Mendelian randomization(MR)method.Methods:This study was based on gene-wide association study(GWAS)summary data,con-structing instrumental variables(IV)using single nucleotide polymorphisms(SNPs).We respectively adopt Inverse variance weighted(IVW),MR-Egger mode and Weighted median(WM)mode to assess the causal relation between IL-7/IL-7Rα and AS.In addition,we also conducted sensitivity tests,including the heterogeneity test,the pleiotropy test,the leave-one-out approach and the MR-PRESSO test.Results:IL-7 and IL-7Rα were respectively included in 9 and 5 IVs that could be used for MR analysis.Results of IVW analysis revealed a reliable causal relationship between IL-7 and IL-7Rα and AS[IL-7:P=0.025 2,OR(95%CI)=0.999 4(0.989 1～0.999 9);IL-7Rα:P=0.008 3,OR(95%CI)=1.000 6(1.000 2～1.001 0)].Cochranes Q test(IL-7:P=0.999 7;IL-7Rα:P=0.946 9)showed that all studies had good homogeneity.The results of a leave-one-out sensitivity analysis suggested that causal associations were not strongly influenced by any selected IVs.The intercept of the MR-Egger regression further showed that pleiotropy did not bias the causal effect in this study.Conclusion:Both IL-7 and IL-7Rα have a strong causal relationship with AS,among which IL-7 is a protec-tive factor for AS,and IL-7Rα is a risk factor for AS.