Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate renal fibrosis in diabetic nephropathy by targeting Hedgehog/SMO signaling.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. Currently, there are no effective drugs for the treatment of DN. Although several studies have reported the therapeutic potential of mesenchymal stem cells, the underlying mechanisms remain largely unknown. Here, we report that both human umbilical cord MSCs (UC-MSCs) and UC-MSC-derived exosomes (UC-MSC-exo) attenuate kidney damage, and inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis in streptozotocin-induced DN rats. Strikingly, the Hedgehog receptor, smoothened (SMO), was significantly upregulated in the kidney tissues of DN patients and rats, and positively correlated with EMT and renal fibrosis. UC-MSC and UC-MSC-exo treatment resulted in decrease of SMO expression. In vitro co-culture experiments revealed that UC-MSC-exo reduced EMT of tubular epithelial cells through inhibiting Hedgehog/SMO pathway. Collectively, UC-MSCs inhibit EMT and renal fibrosis by delivering exosomes and targeting Hedgehog/SMO signaling, suggesting that UC-MSCs and their exosomes are novel anti-fibrotic therapeutics for treating DN.

Anti-angiogenic properties of microRNA-29a in preclinical ocular models.

Abnormal neovascularization is an important cause of blindness in many ocular diseases, for which the etiology and pathogenic mechanisms remain incompletely understood. Recent studies have revealed the diverse roles of noncoding RNAs in various biological processes and facilitated the research and development of the clinical application of numerous RNA drugs, including microRNAs. Here, we report the antiangiogenic activity of microRNA-29a (miR-29a) in three animal models of ocular neovascularization. The miR-29a knockout (KO) mice displayed enhanced vessel pruning, resulting in a decreased vascularized area during retinal development. In contrast, miR-29a deletion in adult mice accelerated angiogenesis in preclinical disease models, including corneal neovascularization, oxygen-induced retinopathy, and choroidal neovascularization, while the administration of agomir-29a ameliorated pathological neovascularization. Furthermore, miR-29a exerted inhibitory effects on endothelial cell proliferation, migration, and tube formation capacities. RNA sequencing analysis of retinas from miR-29a KO mice and RNA interference experiments identified platelet-derived growth factor C and several extracellular matrix genes as downstream targets of miR-29a involved in regulating ocular angiogenesis. Our data suggest that miR-29a may be a promising clinical candidate for the treatment of neovascular diseases.

Mycobacterium vaccae alleviates allergic airway inflammation and airway hyper-responsiveness in asthmatic mice by altering intestinal microbiota.

Host immunity can influence the composition of the gut microbiota and consequently affect disease progression. Previously, we reported that a Mycobacterium vaccae vaccine could ameliorate allergic inflammation in asthmatic mice by regulating inflammatory immune processes. Here, we investigated the anti-inflammatory effects of M. vaccae on allergic asthma via gut microbiota modulation. An ovalbumin (OVA)-induced asthmatic murine model was established and treated with M. vaccae. Gut microbiota profiles were determined in 18 BALB/c mice using 16S rDNA gene sequencing and metabolomic profiling was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. Mycobacterium vaccae alleviated airway hyper-reactivity and inflammatory infiltration in mice with OVA-induced allergic asthma. The microbiota of asthmatic mice is disrupted and that this can be reversed with M. vaccae. Additionally, a total of 24 differential metabolites were screened, and the abundance of PI(14:1(9Z)/18:0), a glycerophospholipid, was found to be correlated with macrophage numbers (r = 0.52, p = 0.039). These metabolites may affect chemokine (such as macrophage chemoattractant protein-1) concentrations in the serum, and ultimately affect pulmonary macrophage recruitment. Our data demonstrated that M. vaccae might alleviate airway inflammation and hyper-responsiveness in asthmatic mice by reversing imbalances in gut microbiota. These novel mechanistic insights are expected to pave the way for novel asthma therapeutic strategies.

Association between systemic immune inflammatory/inflammatory response index and hypertension: A cohort study of functional community.

BACKGROUND AND AIMS: In prospective studies, there is limited evidence of the association between inflammation and hypertension. We aimed to explore the relationship between systemic immune inflammatory index (SII)/systemic inflammatory response index (SIRI) and hypertension in a prospective cohort study to identify the best inflammatory cell markers that predict hypertension. METHODS AND RESULTS: This study was conducted in a functional community cohort in Beijing. In 2015, a total of 6003 individuals without hypertension were recruited and followed up until 2021. Using a restriction cubic spline with baseline SII/SIRI as a continuous variable, the dose-response relationship between hypertension and SII/SIRI was explored. Logistic regression was used to analyze the correlation between hypertension and SII/SIRI trajectory groups. At a mean follow-up of 6 years, 970 participants developed hypertension. SII showed a significant nonlinear dose-response relationship with hypertension (P < 0.05). Higher SII/SIRI was associated with an increased risk of hypertension (SII: RR = 1.003, 95%CI: 1.001-1.004; SIRI: RR = 1.228, 95%CI: 1.015-1.486). Both SII and SIRI were more predictive in males than females (SII: 0.698 vs. 0.695; SIRI: 0.686 vs. 0.678). CONCLUSION: Both systemic immune inflammatory index (SII) and systemic inflammatory response Index (SIRI) independently increased the risk of hypertension, and both were effective inflammatory cell indicators that predict the risk of hypertension.

Scutellarin inhibits oleic acid induced vascular smooth muscle foam cell formation via activating autophagy and inhibiting NLRP3 inflammasome activation.

Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived from marigold flowers, exhibits a spectrum of biological activities including anti-inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC-derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)-induced lipid accumulation and the upregulation of adipose differentiation-associated protein Plin2 in a dose- and time-responsive manner. We elucidated that Scu effectively diminishes OA-provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B-II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA-induced decrement of LC3B-II levels in the presence of bafilomycin-a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross-sectional area, wall-to-lumen ratio and serum total cholesterol levels in comparison to the high-fat diet model group. Collectively, our findings suggest that Scu attenuates OA-induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation.

Molecular engineering of PETase for efficient PET biodegradation.

The widespread utilization of polyethylene terephthalate (PET) has caused a variety of environmental and health problems. Compared with traditional thermomechanical or chemical PET cycling, the biodegradation of PET may offer a more feasible solution. Though the PETase from Ideonalla sakaiensis (IsPETase) displays interesting PET degrading performance under mild conditions; the relatively low thermal stability of IsPETase limits its practical application. In this study, enzyme-catalysed PET degradation was investigated with the promising IsPETase mutant HotPETase (HP). On this basis, a carbohydrate-binding module from Bacillus anthracis (BaCBM) was fused to the C-terminus of HP to construct the PETase mutant (HLCB) for increased PET degradation. Furthermore, to effectively improve PET accessibility and PET-degrading activity, the truncated outer membrane hybrid protein (FadL) was used to expose PETase and BaCBM on the surface of E. coli (BL21with) to develop regenerable whole-cell biocatalysts (D-HLCB). Results showed that, among the tested small-molecular weight ester compounds (p-nitrophenyl phosphate (pNPP), p-Nitrophenyl acetate (pNPA), 4-Nitrophenyl butyrate (pNPB)), PETase displayed the highest hydrolysing activity against pNPP. HP displayed the highest catalytic activity (1.94 µM(p-NP)/min) at 50 °C and increased longevity at 40 °C. The fused BaCBM could clearly improve the catalytic performance of PETase by increasing the optimal reaction temperature and improving the thermostability. When HLCB was used for PET degradation, the yield of monomeric products (255.7 µM) was ∼25.5 % greater than that obtained after 50 h of HP-catalysed PET degradation. Moreover, the highest yield of monomeric products from the D-HLCB-mediated system reached 1.03 mM. The whole-cell catalyst D-HLCB displayed good reusability and stability and could maintain more than 54.6 % of its initial activity for nine cycles. Finally, molecular docking simulations were utilized to investigate the binding mechanism and the reaction mechanism of HLCB, which may provide theoretical evidence to further increase the PET-degrading activities of PETases through rational design. The proposed strategy and developed variants show potential for achieving complete biodegradation of PET under mild conditions.

Examination of learning ability development through the implementation of the "autonomy-collaboration" learning mode grounded in evidence-based medicine practice.

OBJECTIVE: Currently, there are still some shortcomings in EBM education in China.The study aimed to investigate the effectiveness of the novel evidence-based medicine (EBM) learning model of "autonomy-collaboration." METHODS: A total of 91 undergraduate students majoring in clinical medicine at Zhongshan Clinical College of Dalian University from the 2019 batch were selected as the participants in this study. They were instructed to follow the EBM learning model of "autonomy-collaboration." Upon completion of the course, questionnaires, records of participants' sentiments and insights, and evidence-based clinical practice reports were used as indicators to evaluate the effectiveness of the training. RESULTS: This learning modality effectively enhanced independent learning ability of the students, stimulated their interest in learning, and strengthened the communication between students and teachers, thereby improving the quality of teaching. CONCLUSION: The novel EBM learning model of "autonomy-collaboration," exhibited robust effectiveness in instruction and facilitated the seamless integration of theoretical knowledge with clinical practice. Consequently, its widespread adoption is strongly recommended.

Investigation of pollutants accumulation in the submerged zone for pyrite-based bioretention facilities under continuous rainfall events.

Submerged zone in bioretention facilities for stormwater treatment has been approved to be an effective structure amendment to improve denitrification capability. However, the role and influence of water quality changes in the submerged zone under natural continuous random rainfall patterns are still not clear, especially when the rainfall is less than the pore water in the submerged zone. In this study, continuous rainfall events with different rainfall volume (light rain-light rain-heavy rain) were designed in a lab-scale woodchip mulched pyrite bioretention facility to test the effects of rainfall pattern. The results exhibited that light rain events significantly affected the pollutant removal performance of bioretention for the next rainfall. Different effects were observed during the long-term operation. In the 5th month, light rain reduced the ammonia removal efficiency of subsequent rainstorm events by 8.70%, while in the 12th month, when nitrate leakage occurred, light rain led to a 40.24% reduction in the next heavy rain event's nitrate removal efficiency. Additionally, light rain would also affect the concentration of by-products in the next rainfall. Following a light rain, the concentration of sulfate in the subsequent light rainfall can increase by 24.4 mg/L, and by 11.92 mg/L in a heavy rain. The water quality in the submerged zone and media characteristics analysis suggested that nitrogen conversion capacity of the substrate and microbes, such as Nitrospira (2.86%) and Thiobacillus (35.71%), as well as the in-situ accumulation of pollutants under light rain played important roles. This study clarifies the relationship between successive rainfall events and provides a more comprehensive understanding of bioretention facilities. This is beneficial for field study of bioretention facilities in the face of complex rainfall events.

CircRNA hsa_circ_0071336 is associated with type 2 diabetes through targeting the miR-93-5p/GLUT4 axis.

Glucose transporter 4 (GLUT4) is a dominant regulator of whole-body glucose homeostasis. Accumulating evidence has shown that circular RNAs (circRNAs) play significant roles in the pathogenesis of disease. The aim of the present study was to identify the circRNA that can be used as a novel biomarker for type 2 diabetes (T2D) through regulating GLUT4. Based on previous microarray analysis comparing T2D cases and healthy controls, hsa_circ_0071336, which was predicted to be a regulator of GLUT4 by acting as a competitive endogenous RNAs (ceRNA) to sponge miR-93-5p, was selected for further validation. The clinical significance of circulating hsa_circ_0071336 was investigated in a large independent cohort. The results showed that circulating hsa_circ_0071336 was significantly downregulated in blood in T2D and had a high diagnostic accuracy for discriminating T2D and impaired fasting glucose (IFG) from healthy controls. Low expression of circ_0071336 was an independent predictor of T2D, IFG and insulin resistance. A luciferase reporter assay and western-blot analysis indicated that miR-93-5p was a direct target of hsa_circ_0071336, and miR-93-5p may negatively regulate the expression of GLUT4. The expression levels of hsa_circ_007136 were negatively related to miR-93-5p expression and positively correlated with the mRNA expression of GLUT4 in adipose tissues. In conclusion, hsa_circRNA_0071336 can be considered as a potential novel and stable biomarker for T2D and its early detection. hsa_circ_0071336 regulates the GLUT4 expression by sponging miR-93-5p and maybe involved in the pathogenesis of T2D. These findings may unveil new targets for the prevention, diagnosis and treatment of T2D.

Photochemical Selective Oxidation of Benzyl Alcohols to Aldehydes or Ketones.

Using Eosin Y as a metal-free photocatalyst and O2 as an oxidant, the present study reports a new photochemical protocol that enables efficient aerobic oxidation of various benzyl alcohols to the corresponding aldehydes or ketones in excellent yields under mild reaction conditions. The catalyst system presents good functional-group tolerance and exquisite chemoselectivity, which also can easily be scaled-up to gram scale. Moreover, the methodological applications in practical synthesis of several organic molecules and the primary reaction mechanism were also discussed.

RNA-targeted small-molecule drug discoveries: a machine-learning perspective.

In the past two decades, machine learning (ML) has been extensively adopted in protein-targeted small molecule (SM) discovery. Once trained, ML models could exert their predicting abilities on large volumes of molecules within a short time. However, applying ML approaches to discover RNA-targeted SMs is still in its early stages. This is primarily because of the intrinsic structural instability of RNA molecules that impede the structure-based screening or designing of RNA-targeted SMs. Recently, with more studies revealing RNA structures and a growing number of RNA-targeted ligands being identified, it resulted in an increased interest in the field of drugging RNA. Undeniably, intracellular RNA is much more abundant than protein and, if successfully targeted, will be a major alternative target for therapeutics. Therefore, in this context, as well as under the premise of having RNA-related research data, ML-based methods can get involved in improving the speed of traditional experimental processes. [Figure: see text].

Synthesis, antiproliferative and anti-MDR activities of lathyrane diterpene derivatives based on configuration inversion strategy.

A series of lathyrane-type Euphorbia diterpene derivatives featured 3R configuration (H-3ß) were synthesized from natural rich Euphorbia factor L3via modified Mitsunobu reaction based on configuration inversion strategy. The antiproliferation activity and MDR reversal ability of the lathyrane derivatives were evaluated, and the most synthesized compounds showed moderate or strong potencies. Among them, diterpenes 21 (IC50 values of 2.6, 5.2 and 13.1 µM, respectively) and 25 (IC50 values of 5.5, 8.6 and 1.3 µM, respectively) presented the strong cytotoxicity against MCF-7, 4 T1 and HepG2 cells. Meanwhile, derivative 25 exhibited excellent MDR reversal ability with the reversal fold of 16.1 higher than that of verapamil. The cellular thermal shift assay and molecular docking proved direct engagement of diterpene 25 to ABCB1, suggesting 25 could be a promising MDR modulator. Furthermore, the preliminary SARs of these diterpenes were also discussed.

Plasma 8-OHdG act as a biomarker for steroid-induced osteonecrosis of the femoral head.

BACKGROUND: Oxidative stress was closely related to the occurrence and development of Steroid-induced osteonecrosis of the femoral head (SIONFH). 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a important index of oxidative stress. The aim of this study is to investigate the role of 8-OHdG in the development of SIONFH. METHODS: From May 2021 and November 2021, 33 patients diagnosed with SIONFH and 26 healthy controls were recruited in this study. Assessment included the radiography and pathology evaluation of clinical bone tissue, expression position and level of 8-OHdG, level of plasma 8-OHdG, as well as the receiver operating characteristic (ROC) curve. RESULTS: We observed that expression levels of 8-OHdG in bone samples decreased with Association Research Circulation Osseous (ARCO) stages. Plasma 8-OHdG levels were significantly increased in the SIONFH group compared to the healthy control group. Plasma 8-OHdG level of pre-collapse patients was higher than that of post-collapse patients, the decreased plasma 8-OHdG level was related to higher ARCO stages. CONCLUSION: Plasma 8-OHdG may represent potential biomarkers during SIONFH at different stages. Higher plasma 8-OHdG levels indicated early stage of SIONFH. The current study provided new clues for early diagnosis and treatment for SIONFH.

Factors Associated with Lesion Recurrence Following Cervical Conization.

Objective: To investigate the factors influencing lesion recurrence during the follow-up after cervical conization and evaluate the clinical value of human papillomavirus (HPV) testing and thinprep cytology test (TCT) in postoperative follow-up patients undergoing cervical conization. Methods: A total of 289 patients with cervical lesions who underwent primary cervical conization at our hospital between January 1, 2018, and December 31, 2019, were included in this study. TCT, HPV testing, and colposcopy were performed every 6 months for a follow-up period of 3 years. Based on the follow-up results, the patients were divided into recurrence and non-recurrence groups. The basic and colposcopic data of the two groups were analyzed to identify factors influencing lesion recurrence. Additionally, the clinical value of HPV testing and TCT in postoperative follow-up and recurrence diagnosis of patients undergoing cervical conization was assessed. Results: The recurrence group showed significantly higher age of onset, concurrent rate of other chronic diseases, and parity, as well as a markedly lower barrier contraceptive rate compared to the non-recurrence group, with statistically significant differences (P < .05). In the recurrence group, the type III transformation zone (TZ) predominated (59.26%), which significantly differed from the non-recurrence group (P < .05). The detection rates of abnormal TCT findings and HPV infections in postoperative reexaminations were significantly higher in the recurrence group compared to the non-recurrence group (P < .05), whereas no significant differences were observed between the two groups before cervical conization (P > .05). Among the recurrence group (n = 54), 52 cases (96.3%) had HPV infections, and 29 cases (53.7%) had abnormal TCT findings, with a significantly higher detection rate for HPV infections (P < .05). The area under the receiver operating characteristic (ROC) curve (AUC) for HPV testing, TCT, and combined HPV testing with TCT after cervical conization were 0.861, 0.712, and 0.882, respectively. These results indicate that HPV testing alone performs similarly to combined HPV testing with TCT and significantly outperforms TCT alone in predicting lesion recurrence after cervical conization. Conclusions: Factors influencing lesion recurrence after cervical conization include patient age, barrier contraceptive rate, concurrent rate of other chronic diseases, parity, and type of transformation zone. HPV testing alone is more sensitive and accurate than TCT in predicting lesion recurrence during postoperative follow-up of patients undergoing cervical conization. This finding can reduce missed diagnoses and provide a significant theoretical basis for postoperative follow-up of patients undergoing cervical conization.

Automatic literature screening using the PAJO deep-learning model for clinical practice guidelines.

BACKGROUND: Clinical practice guidelines (CPGs) are designed to assist doctors in clinical decision making. High-quality research articles are important for the development of good CPGs. Commonly used manual screening processes are time-consuming and labor-intensive. Artificial intelligence (AI)-based techniques have been widely used to analyze unstructured data, including texts and images. Currently, there are no effective/efficient AI-based systems for screening literature. Therefore, developing an effective method for automatic literature screening can provide significant advantages. METHODS: Using advanced AI techniques, we propose the Paper title, Abstract, and Journal (PAJO) model, which treats article screening as a classification problem. For training, articles appearing in the current CPGs are treated as positive samples. The others are treated as negative samples. Then, the features of the texts (e.g., titles and abstracts) and journal characteristics are fully utilized by the PAJO model using the pretrained bidirectional-encoder-representations-from-transformers (BERT) model. The resulting text and journal encoders, along with the attention mechanism, are integrated in the PAJO model to complete the task. RESULTS: We collected 89,940 articles from PubMed to construct a dataset related to neck pain. Extensive experiments show that the PAJO model surpasses the state-of-the-art baseline by 1.91% (F1 score) and 2.25% (area under the receiver operating characteristic curve). Its prediction performance was also evaluated with respect to subject-matter experts, proving that PAJO can successfully screen high-quality articles. CONCLUSIONS: The PAJO model provides an effective solution for automatic literature screening. It can screen high-quality articles on neck pain and significantly improve the efficiency of CPG development. The methodology of PAJO can also be easily extended to other diseases for literature screening.

Synthesis and Cytotoxicity Evaluation of Dehydroepiandrosterone Derivatives by Iron-Catalyzed Stereoselective Hydroamination.

The direct modification of structurally complex natural product dehydroepiandrosterone (DHEA) through iron-catalyzed direct hydroamination of DHEA with various nitro(hetero)arenes was carried out to afford 5α-arylamino-DHEAs (1-25) in good yields (53-72%). Though as a radical reaction, it features high stereoselectivity, and only the 5α-substituted derivatives were produced. The in vitro antiproliferative activity of these synthesized compounds against the human breast cancer MCF-7 cell was evaluated, showing that most of DHEA analogues possessed the moderate cytotoxic activity. The preliminary structure-activity relationship analysis revealed that the electron-withdrawing groups installed at the para-position of arylamine ring had a great contribution to the improvement of the DHEA's cytotoxic potency. Among them, (4-trifluoromethylaniline)-DHEA (4) displayed the most potent cytotoxicity, with an IC50 value of 19.3 µM, which was 2.3-fold more active than DHEA.

Optimal treatment options for uterine submucosal fibroids: Percutaneous microwave ablation versus transcervical resection of myoma.

OBJECTIVES: To compare the efficacy and safety of percutaneous microwave ablation (PMWA) and transcervical resection of myoma (TCRM) for submucosal fibroids. METHODS: From January 2019 to January 2021, we conducted a randomized controlled study involving patients with symptomatic uterine submucosal fibroids. Questionnaires were also used to measure the uterine fibroid symptom (UFS) scores and quality of life (QoL) scores before and after treatment at 3, 6, and 12 months. Outcomes, adverse events, hemoglobin recovery, and submucosal fibroid volume of both groups were also compared. Operation time, amount of bleeding, hospital stay time, and occurrence of complications were compared in groups with fibroids of different lengths. RESULTS: Follow-up after surgery showed that UFS scores at 3, 6, and 12 months were significantly lower in each group, while QoL scores increased significantly. For fibroids less than 3 cm, surgical time was 34.2 ± 9.9 min, incidence of perioperative complications was 4.2%, and both decreased significantly, compared to the surgical time of the PMWA group (40.0 ± 8.1 min) and incidence of perioperative complications (24%; p < .05 for both). For uterine submucosal fibroids >5 cm, the operation time in the PMWA group was 92.7 ± 16.0 min, intraoperative bleeding volume was 22.7 ± 6.4 mL, and hospital stay was 2.7 ± 1.1 days, which were significantly less than the procedural time (107 ± 11.9 min), intraoperative bleeding loss (45.9 ± 12.8 mL), and length of hospital stay (5.0 ± 1.1 days) in the TCRM group. The differences were statistically significant (p < .05). CONCLUSIONS: PMWA and TCRM were both effective treatments for uterine submucosal fibroids. For fibroids shorter than 3 cm in length, especially pedicled submucosal fibroids, TCRM has absolute advantages; however, for uterine submucosal fibroids >5 cm, PMWA avoids perioperative complications, such as uterine perforation, water poisoning syndrome, and the need for repeat surgery, and is considered the preferred mode of treatment. Therefore, personalized treatment should be used for different patients with uterine submucosal fibroids.

Using Normalized Carcinoembryonic Antigen and Carbohydrate Antigen 19 to Predict and Monitor the Efficacy of Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are established prognostic biomarkers for patients with gastric cancer. However, their potential as predictive markers for neoadjuvant chemotherapy (NACT) efficacy has not been fully elucidated. METHODS: We conducted a retrospective analysis to determine values of CEA and CA19-9 prior to NACT (pre-NACT) and after NACT (post-NACT) in 399 patients with locally advanced gastric cancer (LAGC) who received intended NACT and surgery. RESULTS: Among the 399 patients who underwent NACT plus surgery, 132 patients (33.1%) had elevated pre-NACT CEA/CA19-9 values. Furthermore, either pre-NACT or post-NACT CEA /CA19-9 levels were significantly associated with prognosis (p = 0.0023) compared to patients with non-elevated levels. Moreover, among the patients, a significant proportion (73/132, 55.3%) achieved normalized CEA/CA19-9 following NACT, which is a strong marker of a favorable treatment response and survival benefits. In addition, the patients with normalized CEA/CA19-9 also had a prolonged survival compared to those who underwent surgery first (p = 0.0140), which may be attributed to the clearance of micro-metastatic foci. Additionally, the magnitude of CEA/CA19-9 changes did not exhibit a statistically significant prognostic value. CONCLUSIONS: Normalization of CEA/CA19-9 is a strong biomarker for the effectiveness of treatment, and can thus be exploited to prolong the long-term survival of patients with LAGC.

Bismacrocycle: Structures and Applications.

In the past half-century, macrocycles with different structures and functions, have played a critical role in supramolecular chemistry. Two macrocyclic moieties can be linked to form bismacrocycle molecules. Compared with monomacrocycle, the unique structures of bismacrocycles led to their specific recognition and assembly properties, also a wide range of applications, including molecular recognition, supramolecular self-assembly, advanced optical material construction, etc. In this review, we focus on the structure of bismacrocycle and their applications. Our goal is to summarize and outline the possible future development directions of bismacrocycle research.

An investigation on information quality, media richness, and social media fatigue during the disruptions of COVID-19 pandemic.

Mobile social platforms have become a valuable information source by which users gain information about the COVID-19 pandemic. However, little is known about whether users have experienced increased daily fatigue as a result of the disruptions caused by pandemic. Drawing on the cognitive activation theory of stress (CATS), this study proposed that two typical characteristics of social media platforms (SMP), information quality and media richness, are associated with event disruptions of the COVID-19 pandemic (EDC), and then induce social media fatigue. To address this, this study used the experience sampling method (ESM), collecting 550 matched cases from 110 users of the WeChat application in mainland China over five consecutive days. Through multilevel structural equation modeling (MSEM), this study discovered three main findings: (1) daily information quality is negatively related to event disruptions of the COVID-19 pandemic, which in turn decreases daily social media fatigue; (2) daily media richness is positively associated with such event disruptions, which ultimately increases daily social media fatigue; (3) these effects were stronger for users who reported higher (vs. lower) levels of health consciousness. The implications of these results for the COVID-19 pandemic and beyond are discussed.