Objective To compare the early clinical effects of unilateral biportal endoscopic lumbar in-terbody fusion(ULIF)and minimally invasive transforaminal lumbar interbody fusion(MIS-TLIF)in the treatment of single lumbar degenerative disease(LDD).Methods The patients with LDD treated with ULIF(ULIF group,n=32)and MIS-TLIF(MIS-TLIF group,n=36)in this hospital from January 2020 to Novem-ber 2022 were selected as the study subjects.The perioperative conditions were compared between the two groups,including the postoperative drainage volume,postoperative ground activity time,hospitalization dura-tion,total hospitalization expenses,laboratory hematological indexes including Hb,HCT,CRP and CK levels.The clinical effects were compared between the two groups,including the visual analogue scale(VAS)score of waist and leg pain,Oswestry dysfunction index(ODI),operation excellence rate,vertebral fusion rate and op-eration related complications.Results Compared with the MIS-TLIF group,the ULIF group had less postop-erative drainage,earlier ground activity time,short hospitalization duration,but the operation time was longer and hospitalization costs were higher,and the differences were statistically significant(P<0.05).Compared with the MIS-TLIF group,the Hb and HCT levels on postoperative 3 d in the ULIF group were higher,the CRP and CK levels on postoperative 1,3,5 d were lower,and the differences were statistically significant(P<0.05).The waist and leg pain VAS score and ODI at each postoperative follow up time points in the two groups were significantly improved compared with before operation(P<0.05).The intergroup comparison showed that the VAS score in postoperative 1 week and 1 month,and ODI in postoperative 1 month in the ULIF group were lower than those in the MIS-TLIF group(P<0.05).In postoperative 12 months,the opera-tion excellence rate and intervertebral fusion rate in the ULIF group were 93.75%and 96.88%respectively,which in the MIS-TLIF group were 88.89%and 91.67%respectively,but the difference between the two groups were not statistically significant(P>0.05).Conclusion Adopting ULIF in the treatment of single LDD could obtain the similar clinical effectt of MIS-TLIF,moreover ULIF has less tissue damage,less bleed-ing,less inflammatory reaction and faster postoperative recovery.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Objective To explore the feasibility, safety, and efficacy of transesophageal endoscopic surgery for mediastinal tumors. Methods A retrospective analysis was conducted on the clinical data of 17 patients who underwent transesophageal endoscopic resection for benign mediastinal tumors at the Endoscopy Center of Zhongshan Hospital, Fudan University, between January 1, 2016 and December 31, 2024. Epidemiological characteristics, surgical parameters, adverse events, and follow-up outcomes were analyzed. Results Among the 17 patients, there were 9 males and 8 females, with an average age of (42.4±14.5) years and an average tumor size of (2.6±1.6) cm. Pathological types included esophageal duplication cysts (6 cases, 35.3%), bronchogenic cysts (5 cases, 29.4%), gastroenteric cysts (3 cases, 17.6%), schwannomas (2 cases, 11.8%), and lymphangioma (1 case, 5.9%). Fourteen patients (82.4%) underwent submucosal tunneling endoscopic resection (STER), 3 patients (17.6%) underwent natural orifice transluminal endoscopic mediastinal surgery. All surgeries were successfully completed without conversion to open surgery. En bloc resection was achieved in 11 patients (64.7%), with an average operative time of (60.9±32.6) min. No intraoperative bleeding or mucosal injury occurred, and 4 patients (23.5%) experienced minor complications (pneumothorax, fever, recurrent laryngeal nerve injury), all of which resolved with conservative treatment. The average postoperative hospital stay was (3.2±1.5) days, and no recurrence was observed during the follow-up period. Conclusions Transesophageal endoscopic resection of benign mediastinal tumors is a safe, effective, and minimally invasive treatment method. Further validation of its efficacy and safety through large-scale prospective studies is warranted.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， the combination of serum pharmacochemistry， response profile of absorbed components in serum， network pharmacology and drug-likeness prediction was used to screen the potential active ingredients of Yanghetang against breast cancer. MethodsUPLC-Q-TOF-MS/MS was used to identify the main components in different solvent extracts of Yanghetang， and serum pharmacochemistry was applied to analyze the absorbed components from the serum of female SD rats after 0.5， 1， 2 h of administration. Combined with the response characteristic values of serum drug components obtained from UNIFI 1.8.2， the absorbed prototype components and metabolites were screened to get the absorbed components of Yanghetang with a significant patterns of elimination and growth. Network pharmacology was applied to construct a drug-component-pathway-target-disease network， and molecular docking was performed between absorbed components and key targets of breast cancer， and the drug similarity was analyzed by SwissADME. ResultsForty-two compounds were identified in Yanghetang samples extracted with different solvents， of which 16 compounds were common to the three different extraction solvents（methanol， 50% methanol and water）. The results of drug-containing serum analysis showed that there were 16 absorbed components in serum， including 5 prototypes and 11 metabolites. Network pharmacology results showed that Yanghetang against breast cancer involved 15 key targets such as proto-oncogene tyrosine-protein kinase Src（SRC）， epidermal growth factor receptor（EGFR） and phosphoinositide 3 kinase catalytic alpha polypeptide（PIK3CA）. Molecular docking results showed that 16 potential active ingredients were well combined with the predicted targets. Combined with drug likenesses， 12 compounds in the absorbed components of Yanghetang were considered to have potential for anti-breast cancer activity， mainly including α-pinene and γ-eudesmol and their metabolites， of which one was from Ephedrae Herba， one was from Rehmanniae Radix， and eight were from Cinnamomi Cortex. ConclusionThe chemical components of Yanghetang mainly include polysaccharides， monoterpene glycosides and coumarins， and its prototype components mainly undergo oxidation， hydrolysis and acetylation after entering the blood. Its anti-breast cancer mechanism may be related to the regulation of signaling pathways such as the mitogen-activated protein kinase（MAPK） and phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）. The results of this study can lay a foundation for further exploration of Yanghetang in the treatment of breast cancer.

Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System X_c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

Objective:To conduct a survey on the influence of personality trait on depres-sive symptom and obesity in patients before bariatric and metabolic surgery.Methods:The retros-pective cross-sectional investigation study was conducted. Patients who underwent bariatric and metabolic surgery in The Third Xiangya Hospital of Central South University and The First Affiliated Hospital of Ji′nan University from January 1 to June 1,2024 were recruited. The survey was conducted in electronic format using the general information survey questionnaire, the patient health question-naire-9 (PHQ-9), and the Chinese big five personality inventory brief version (CBF-PI-B). Observa-tion indicators: (1) results of the questionnaire; (2) general data of patient; (3) personality trait scores for patient with different subtypes of obesity; (4) depression symptom scores for patient with different subtypes of obesity; (5) correlation analysis for patient personality trait, depressive symptom and body mass index (BMI). Comparison of measurement data with normal distribution between groups was conducted using the independent t test, and one-way analysis of variance was used for comparison among multiple groups. LSD test was used for pairwise comparison. Comparison of measurement data with skewed distribution among multiple groups was conducted using the Kruskal-Wallis H test, and Dunn Bonferroni test was used for pairwise comparison. The Spearman correlation analysis and Pearson correlation analysis were used for correlation analysis, and the mediation effect analysis was conducted using the Process 4.0 model and the Bootstrap test. Results:(1)Results of the questionnaire. A total of 146 questionnaires were distributed and collected, including 83 questionnaires from The Third Xiangya Hospital of Central South University and 63 questionnaires from The First Affiliated Hospital of Ji′nan University. Of 146 questionnaires, 137 questionnaires were valid, yielding an effective response rate of 93.836%(137/146). (2)General data of patient. Of the 137 patients who completed valid questionnaires, 52 were male with BMI of (41±5)kg/m 2, 85 were female with BMI of (38±6)kg/m 2, showing a significant difference between them ( t=2.586, P<0.05). There were 40 patients aged ≤25 years, with BMI of (42±5)kg/m 2, 28 patients aged 26-30 years, with BMI of (39±5)kg/m 2, 49 patients aged 31-40 years, with BMI of (38±6)kg/m 2, 14 patients aged 41-50 years, with BMI of (38±7)kg/m 2, 6 patients aged >50 years, with BMI of (37±3)kg/m 2. There were significant differences in BMI of patients of different age groups ( F=2.697, P<0.05). (3)Persona-lity trait scores for patient with different subtypes of obesity. Of the 137 patients who completed valid questionnaires, there were 15 patients of mild obesity, with personality trait neuroticism score of 19.0(14.0,24.0), personality trait strictness score of 32.5±5.2, personality trait extroversion score of 30.0(24.0,40.0), 36 patients of moderate obesity, with personality trait neuro-ticism score of 26.5(22.3,28.8), personality trait strictness score of 32.6±5.9, personality trait extro-version score of 34.0(26.3,39.0), 81 patients of severe obesity, with personality trait neuroticism score of 35.0(29.5,41.0), personality trait strictness score of 26.8±7.4, personality trait extroversion score of 28.0(20.5,35.0), 5 patients of extreme obesity, with personality trait neuroticism score of 28.0(26.5,44.0), personality trait strictness score of 19.6±3.4, personality trait extroversion score of 22.0(18.5,25.0). There were significant differences in personality trait neuroticism, strictness and extroversion among patients of different subtypes of obesity ( H=50.316, F=10.774, H=14.446, P<0.05). (4)Depression symptom scores for patient with different subtypes of obesity. Of the 137 pati-ents who completed valid questionnaires, the depressive symptom score were 4.0(2.0,9.0) for 15 pati-ents of mild obesity, 5.0(3.0,7.0) for 36 patients of moderate obesity, 13.0(8.5,17.0) for 81 patients of severe obesity, and 18.0(9.5,22.0) for 5 patients of extreme obesity, respectively, showing a significant difference among them ( H=50.129, P<0.05). (5) Correlation analysis for patient personality trait, depressive symptom and BMI. Results of Spearman correlation analysis showed that personality trait neuroticism were positively correlated with depressive symptoms and BMI ( r=0.780, 0.557, P<0.05), personality trait strictness was negatively correlated with depressive symptoms ( r=-0.523, P<0.05), personality trait extroversion were negatively correlated with depressive symptoms and BMI ( r=-0.448, -0.323, P<0.05), and depressive symptoms was positively correlated with BMI ( r=0.568, P<0.05). Results of Pearson correlation analysis showed that personality trait strictness was negatively correlated with BMI ( r=-0.489, P<0.05). Conclusion:Preoperative personality trait of patients undergoing bariatric and metabolic surgery can influence their depressive symptom and BMI.

Objective To explore the biological functions of pyroptosis-related genes in pneumonic plague using bioinformatics methods,and to evaluate their potential applicability as diagnostic markers.Methods The pneumonic plague-related dataset GSE220123 was retrieved from the Gene Expression Omnibus(GEO)database and screened for differentially expressed pyroptosis-related genes(DE-PRGs).The functions of DE-PRGs were studied via Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and immune infiltration analysis.The hub genes were identified via protein-protein interaction(PPI)network analysis,and further screened for key genes with sustained high expression characteristics based on differential expression analysis.The relative expression levels of the key genes were verified using the reverse transcription real-time quantitative PCR(qPCR)method.Results A total of 17 DE-PRGs were screened,and PPI network analysis revealed 7 Hub genes.Among them,Casp4 continued to be up-regulated during the course of pneumonic plague.The results of reverse transcription qPCR were consistent with the those of bioinformatic analyses.Conclusion DE-PRGs play a crucial role in the immune response of pneumonic plague,especially Casp4,which has significant applications as a diagnostic biomarker and potential therapeutic target for pneumonic plague.

Background:Acute pancreatitis(AP)is a common clinical gastrointestinal emergency with a high mortality rate.Intestinal dysfunction is one of the common complications of AP and can aggravate the disease condition.Therefore,early and accurate assessment of the disease severity and intestinal dysfunction of AP is of great significance for improving the prognosis of patients.Aims:To investigate the correlation of early serum levels of interleukin-1β(IL-1β),C-reactive protein(CRP),endotoxin(ET),D-lactic acid(D-LA),and diamine oxidase(DAO)with disease severity and intestinal dysfunction in AP patients.Methods:A total of 52 AP patients admitted to the Second Affiliated Hospital of Baotou Medical College from September 2023 to September 2024 were enrolled,and 10 healthy individuals recruited during the same period were served as the control group.AP patients were classified into mild acute pancreatitis(MAP),moderately severe acute pancreatitis(MSAP)and severe acute pancreatitis(SAP)groups according to the severity of the disease.Intestinal function was evaluated using the acute gastrointestinal injury(AGI)grading system.ELISA was used to detect the early serum levels of IL-1β,CRP,ET,D-LA,and DAO,and the correlation of these indicators with the severity of AP and AGI grade were analyzed by Spearman correlation coefficient.Results:Serum levels of IL-1β,CRP,ET,D-LA,and DAO in the MAP,MSAP,and SAP groups were significantly higher than those in the control group(all P<0.05);serum levels of IL-1β,CRP,ET,D-LA,and DAO in the MSAP group were significantly higher than those in the MAP group(all P<0.05);serum levels of IL-1β,CRP,ET,D-LA,and DAO in the SAP group were significantly higher than those in the MAP and MSAP groups(all P<0.05).Compared with AGI grade 0-Ⅰ subjects,serum levels of IL-1β,CRP,ET,D-LA,and DAO in patients with AGI grade Ⅱ,Ⅲ and Ⅳ were significantly increased(all P<0.05).Compared with AGI grade Ⅱ patients,serum D-LA level in patients with AGI grade Ⅲ was significantly increased(P<0.05).Compared with AGI grade Ⅲ patients,serum D-LA level in patients with AGI grade Ⅳ was significantly increased(P<0.05).Serum levels of IL-1β,CRP,ET,D-LA,and DAO were positively correlated with the severity of AP and AGI grade(all P<0.05).Conclusions:Early serum levels of IL-1β,CRP,ET,D-LA,and DAO in AP patients are significantly increased and closely related to the disease severity and intestinal dysfunction.