Association of myopia and astigmatism with postoperative ocular high order aberration after small incision lenticule extraction.

OBJECTIVE: To investigate the correlation between higher-order aberrations (HOA) after small incision lenticule extraction (SMILE) and the severity of myopia and astigmatism, along with the relevant factors. These findings will provide valuable insights for decreasing the occurrence of HOA after SMILE and enhancing visual quality. METHODS: A total of 75 patients (150 eyes) with myopia and astigmatism who underwent SMILE were categorized into four groups based on the severity of myopia and astigmatism: Myopia Group 1 (Group M1, spherical diopter ranged from -1.00 D to -4.00 D), Myopia Group 2 (Group M2, spherical diopter ranged from -4.10 D to -10.00 D), Astigmatism Group 1 (Group A1, cylindrical diopter ranged from 0 D to -1.00 D), and Astigmatism Group 2 (Group A2, cylindrical diopter ranged from -1.10 D to -3.00 D). A comprehensive assessment was performed to examine the association between HOA and various relevant factors, including a detailed analysis of the subgroups. RESULTS: Group M1 had significantly lower levels of total eye coma aberration (CA), corneal total HOA (tHOA), internal tHOA, and vertical CA ( Z 3 - 1 ) after SMILE than Group M2 (P < 0.05). Similarly, Group A1 had significantly lower levels of total eye tHOA, CA, trefoil aberration (TA), corneal tHOA, TA, and vertical TA ( Z 3 - 3 ) after SMILE than Group A2 (P < 0.05). Pearson correlation analysis indicated a statistically significant positive relationship between the severity of myopia/astigmatism and most HOA (P < 0.05). Subgroup evaluations demonstrated a notable increase in postoperative HOA associated with myopia and astigmatism in Groups M2 and A2 compared with the control group. Lenticule thickness, postoperative central corneal thickness (CCT), postoperative uncorrected distance visual acuity (UDVA), and postoperative corneal Km and Cyl were strongly correlated with most HOA. Age, eyes, and postoperative intraocular pressure (IOP) were only associated with specific HOA. CONCLUSION: HOA positively correlated with the severity of myopia and astigmatism after SMILE. However, this relationship was not linear. HOA after SMILE was influenced by various factors, and additional specialized investigations are required to establish its clinical importance.

Design and characterization of Fe(II) complexes with tetradentate ligands exhibiting spin-crossover near room temperature.

Construction of spin-crossover (SCO) materials is very appealing for applications such as molecular switches and information storage. This study focuses on the design of Fe(II) complexes using N,N'-bis(2-pyridinylmethyl)-1,2-ethanediamine-based ligands with an N4 structure for SCO material development. By incorporating para-substituted benzene groups into the ligand's pyridine moiety, two polymorphs, α and ß, were obtained, both exhibiting SCO activity. Notably, the ß polymorph displayed a spin crossover temperature of 270 K, which is approaching room temperature. Structural analyses were conducted to compare the differences between the polymorphs, along with a literature review of related complexes, providing insights into the characteristics of SCO behavior.

Associations between non-insulin-based insulin resistance indices and heart failure prevalence in overweight/obesity adults without diabetes mellitus: evidence from the NHANES 2001-2018.

BACKGROUND: The triglyceride glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio are recognized as simple non-insulin-based insulin resistance indices. Our study aimed to explore the relationship between these two indicators and heart failure (HF) in overweight or obesity individuals without diabetes. METHODS: This cross-sectional study selected 13,473 participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2018 dataset. Weighted multivariable logistic regression and subgroup analysis were employed to evaluate the relationships between TyG index, TG/HDL-C ratio, and HF prevalence, respectively. Additionally, smooth curve fitting was utilized to analyze the dose-response relationships. RESULTS: A total of 13,473 obesity or overweight people without diabetes were included in this study through screening, among whom 291 (2.16%) had comorbid HF. The results of multivariable logistic regression suggested that the highest TyG index (OR = 2.4, 95% CI = 1.4-4.2, p = 0.002) and the highest TG/HDL-C ratio (OR = 1.2, 95% CI = 1.1-1.3, p < 0.001) both increased the prevalence of HF, especially in the non-Hispanic population. Dose-response relationships suggested nonlinear relationships between these two indicators and HF. CONCLUSION: Our study demonstrated that elevated TyG index and TG/HDL-C ratio were closely associated with the prevalence of HF, and both exhibited nonlinear relationships with HF prevalence in overweight/obesity adults without diabetes. Based on these findings, additional prospective studies are needed for further validation.

Differences in ocular high order aberrations before and after small incision lenticule extraction for correction of myopia: a systematic review and meta-analysis.

Objective: To examine the causes and factors that lead to high order aberration (HOA) during the treatment of myopia using small incision lenticule extraction (SMILE), as well as the differences between SMILE and other corneal refractive surgeries through a systematic review and meta-analysis. Methods: A systematic search was conducted from January 2015 to February 2023 in Pubmed, Embase, Web of Science, and Google Scholar databases to gather relevant studies on SMILE and HOA. Studies meeting specific criteria were chosen, and clinical data was retrieved for analysis. Results: This meta-analysis resulted in the inclusion of 19 studies involving 1,503 eyes. Pooled results showed significant induction of total HOA (tHOA, d = -0.21, p < 0.001), spherical aberration (SA, d = -0.11, p < 0.001) and coma aberration (CA, d = -0.18, p < 0.001) after SMILE compared to pre-SMILE, while no significant change in trefoil aberration (TA) was observed (d = -0.00, p = 0.91). There was a significantly lower induction of tHOA after SMILE compared to femtosecond laser-assisted in situ keratomileusis (FS-LASIK, d = 0.04, p < 0.001), and no significant difference was observed compared to wavefront aberration-guided (WFG) refractive surgery (d = 0.00, p = 0.75). There was also a significant association between different levels of myopia and astigmatism, duration of follow-up, lenticule thickness, and preoperative central corneal thickness (CCT) on the induction of tHOA after SMILE (p < 0.05), while the higher preoperative myopia group (sphere > -5D), lower preoperative astigmatism group (cylinder ≤ -1D), larger lenticule thickness group (lenticule thickness > 100 µm), shorter follow-up group (follow-up 1 month postoperatively) and the thicker CCT group (CCT > 550 µm) brought a significant induction of tHOA compared to the opposite comparison group (p < 0.001). Conclusion: While SMILE can induce HOA significantly, it induces less HOA than FS-LASIK. Postoperative HOA following SMILE can be affected by factors such as myopia, astigmatism, lenticule thickness, CCT, and duration of follow-up. Future research should continue to explore techniques to decrease the induction of HOA by using this methodology. Systematic review registration: https://www.crd.york.ac.uk/prospero/.

Changes of dry eye parameters after small incision lenticule extraction surgery in patients with different ocular surface disease index scores.

To evaluate the changes of dry eye parameters after small incision lenticule extraction (SMILE) surgery in patients with different ocular surface disease index (OSDI) scores. Prospective research. Participants were divided into two groups: Group A, OSDI < 13; and Group B, OSDI ≥ 13. The OSDI scores, tear meniscus height (TMH), first non-invasive tear film break-up time (NIBUT-First), and meibomian gland loss (MGL, %) were recorded at postoperative 1 -week and 1-month.113 eyes (57 patients) were enrolled, 70 eyes in Group A, and 43 eyes in Group B. In Group A, the OSDI scores significantly increased at 1-week and 1-month postoperative (all P < 0.001); the TMH, NIBUT-First and lipid layer grade significantly decreased at postoperative 1-week (P = 0.003, 0.005, 0.007, 0.004, respectively), but returned to preoperative level at 1-month postoperative. In Group B, only the lipid layer grade significantly decreased at postoperative 1-week (P < 0.05). Patients with different preoperative OSDI scores may experience different changes early after SMILE surgery. Patients with OSDI scores < 13 may experience more dramatic changes in dry eye symptoms which would resolve, while subjective complains could still exists at 1 month after surgery.

Predicting Implantable Collamer Lens Vault Using Machine Learning Based on Various Preoperative Biometric Factors.

Purpose: To predict the vault size after Implantable Collamer Lens (ICL) V4c implantation using machine learning methods and to compare the predicted vault with the conventional manufacturer's nomogram. Methods: This study included 707 patients (707 eyes) who underwent ICL V4c implantation at the Department of Ophthalmology, Peking Union Medical College Hospital, from September 2019 to January 2022. Random Forest Regression (RFR), XGBoost, and linear regression (LR) were used to predict the vault size 1 week after ICL V4c implantation. The mean absolute error (MAE), median absolute error (MedAE), root mean square error (RMSE), symmetric mean absolute percentage error (SMAPE), and Bland-Altman plot were utilized to compare the prediction performance of these machine learning methods. Results: The dataset was divided into a training set of 180 patients (180 eyes) and a test set of 527 patients (527 eyes). XGBoost had the lowest prediction error, with mean MAE, RMSE, and SMAPE values of 121.70 µm, 148.87 µm, and 19.13%, respectively. The Bland‒Altman plots of RFR and XGBoost showed better prediction consistency than LR. However, XGBoost showed narrower 95% limits of agreement (LoA) than RFR, ranging from -307.12 to 256.59 µm. Conclusions: XGBoost demonstrated better predictive performance than RFR and LR, as it had the lowest prediction error and the narrowest 95% LoA. Machine learning may be applicable for vault prediction, and it might be helpful for reducing the complications and the secondary surgery rate. Translational Relevance: Using the proposed machine learning model, surgeons can consider the postoperative vault to reduce the surgical complications.

Quality evaluation of Chinese and global guidelines/consensus for TDM of anti-TNF-α agents in patients with inflammatory bowel disease / 中国药房

OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring （TDM） of anti-tumor necrosis factor-α （TNF-α） in patients with inflammatory bowel disease （IBD） in China and globally. METHODS PubMed， Embase， CNKI， Wanfang data， VIP， and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data， the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included， 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions （scope and aims， participants， rigor of formulation， clarity of expression， application， and editorial independence） were 90.43%， 41.98%， 52.55%， 85.49%， 19.00%， and 76.85%， respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios， threshold ranges， strategy adjustments， detection methods， and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally， the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair， with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs， and interpret and apply results of TDM in combination with specific clinical treatment goals.

Prediction of EGFR mutation status in lung adenocarcinoma based on 18F-FDG PET/CT radiomic features.

The earlier identification of EGFR mutation status in lung adenocarcinoma patients is crucial for treatment decision-making. Radiomics, which involves high-throughput extraction of imaging features from medical images for quantitative analysis, can quantify tumor heterogeneity and assess tumor biology non-invasively. This field has gained attention from researchers in recent years. The aim of this study is to establish a model based on 18F-FDG PET/CT radiomic features to predict the epidermal growth factor receptor (EGFR) mutation status of lung adenocarcinoma and evaluate its performance. 155 patients with lung adenocarcinoma who underwent 18F-FDG PET/CT scans and EGFR gene detection before treatment were retrospectively analyzed. The LIFEx packages was used to perform 3D volume of interest (VOI) segmentation manually on DICOM images and extract 128 radiomic features. The Wilcoxon rank sum test and least absolute shrinkage and selection operator (LASSO) regression algorithm were applied to filter the radiomic features and establish models. The performance of the models was evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Among the models we have built, the radiomic model based on 18F-FDG PET/CT has the best prediction performance for EGFR gene mutation status, with an AUC of 0.90 (95% CI 0.84~0.96) in the training set and 0.79 (95% CI 0.64~0.94) in the test set. In conclusion, we have established a radiomics model based on 18F-FDG PET/CT, which has good predictive performance in identifying EGFR gene mutation status in lung adenocarcinoma patients.

Reduction in the duration of postoperative fever following NUSS surgery during the COVID-19 pandemic.

BACKGROUND: Our study aimed to compare the prevalence of postoperative fever during the COVID-19 pandemic period with that of the preceding non-pandemic period. METHODS: A retrospective analysis was conducted on patients with pectus excavatum (PE) undergoing minimally invasive repair (also called NUSS procedure) at Nanjing Children's Hospital from January 1, 2017 to March 1, 2019 (Group 2019), and from January 1, 2020 to March 1, 2021 (Group 2021). Data from a total of 284 patients, consisting of 200 (70.4%) males and 84 (29.6%) females with an average age of 9.73 ± 3.41 (range, 4 to 17) years, were collected. The presence of post-operative fever (defined as a forehead temperature of 37.5℃ or above within 72 h post-surgery), as well as the time of operation, duration of postoperative mechanical ventilator and urinary catheter use, and length of hospitalization were all assessed in admitted patients from Group 2019 (n = 144) and Group 2021 (n = 140). Postoperative white blood cell (WBC), C-reactive protein (CRP) levels, and prevalence of postoperative complications (i.e., pneumothorax, pulmonary atelectasis, pneumonia, wound infection, and dehiscence) were also determined. RESULT: Our results showed a statistically significant decrease in the incidence of postoperative fever within 24 to 72 h of surgery in patients admitted from Group 2019 as compared to Group 2021 (p < 0.001), as well as a decrease in peak body temperature within 72 h (p < 0.05). Meanwhile, no significant differences were observed in age and body mass index (BMI), time of operation, or duration of postoperative mechanical ventilator and urinary catheter use between the two groups (p > 0.05). The average hospitalization length of Group 2021 was significantly shorter than Group 2019 (12.49 ± 2.57 vs. 11.85 ± 2.19 days, p < 0.05). Furthermore, while the WBC count between the two groups 24 h after surgery showed a statistical difference (p < 0.05), no differences in CRP levels or the incidence of postoperative complications were observed (p > 0.05). CONCLUSION: The prevalence of postoperative fever within 72 h of surgery and the length of hospital stay for patients with PE undergoing NUSS surgery were both decreased in Group 2021. We propose that the above phenomenon may be related to increased used of personal protection equipment (such as surgical masks and filtering facepiece respirators (FFRs)) by physicians, nurses, and the patients themselves.

Comparison of the adjuvant effect of conbercept intravitreal injection at different times before vitrectomy for proliferative diabetic retinopathy.

Purpose: To assess the optimal time of intravitreal conbercept (IVC) treatment prior to pars plana vitrectomy (PPV) in patients with severe proliferative diabetic retinopathy (PDR). Method: This study was exploratory in nature. Forty-eight consecutive patients (48 eyes) with PDR were divided into four groups according to different IVC times (0.5 mg/0.05 mL) before PPV: group A (3 days), group B (7 days), group C (14 days), and group D (non-IVC). Intraoperative and postoperative effectiveness were assessed, and vitreous VEGF concentrations were detected. Result: For intraoperative effectiveness, groups A and D had a higher incidence of intraoperative bleeding than groups B and C (P = 0.041). Furthermore, groups A-C required less surgical time than group D (P < 0.05). For postoperative effectiveness, group B had a significantly higher proportion of visual acuity that improved or remained unchanged than group D (P = 0.014), and groups A-C had lower proportions of postoperative bleeding than group D. The vitreous VEGF concentration of group B (67.04 ± 47.24 pg/mL) was significantly lower than that of group D (178.29 ± 110.50 pg/mL) (P = 0.005). Conclusion: IVC treatment that was administered 7 days preoperatively was associated with better effectiveness and a lower vitreous VEGF concentration than its administration at other time points.

Performance of artificial intelligence in diabetic retinopathy screening: a systematic review and meta-analysis of prospective studies.

Aims: To systematically evaluate the diagnostic value of an artificial intelligence (AI) algorithm model for various types of diabetic retinopathy (DR) in prospective studies over the previous five years, and to explore the factors affecting its diagnostic effectiveness. Materials and methods: A search was conducted in Cochrane Library, Embase, Web of Science, PubMed, and IEEE databases to collect prospective studies on AI models for the diagnosis of DR from January 2017 to December 2022. We used QUADAS-2 to evaluate the risk of bias in the included studies. Meta-analysis was performed using MetaDiSc and STATA 14.0 software to calculate the combined sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of various types of DR. Diagnostic odds ratios, summary receiver operating characteristic (SROC) plots, coupled forest plots, and subgroup analysis were performed according to the DR categories, patient source, region of study, and quality of literature, image, and algorithm. Results: Finally, 21 studies were included. Meta-analysis showed that the pooled sensitivity, specificity, pooled positive likelihood ratio, pooled negative likelihood ratio, area under the curve, Cochrane Q index, and pooled diagnostic odds ratio of AI model for the diagnosis of DR were 0.880 (0.875-0.884), 0.912 (0.99-0.913), 13.021 (10.738-15.789), 0.083 (0.061-0.112), 0.9798, 0.9388, and 206.80 (124.82-342.63), respectively. The DR categories, patient source, region of study, sample size, quality of literature, image, and algorithm may affect the diagnostic efficiency of AI for DR. Conclusion: AI model has a clear diagnostic value for DR, but it is influenced by many factors that deserve further study. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023389687.

Combination therapy with 3% diquafosol tetrasodium ophthalmic solution and sodium hyaluronate: an effective therapy for patients with dry eye after femtosecond laser-assisted in situ keratomileusis.

Purpose: To assess the effect of combination therapy with 3% diquafosol tetrasodium (DQS) and sodium hyaluronate (HA) for dry eye after femtosecond laser-assisted in situ keratomileusis (FS-LASIK). Design: Prospective nonrandomized comparative trial. Methods: The prospective study included 80 eyes of 40 patients who underwent FS-LASIK with or without preoperative dry eye. Patients were divided into a combination group and a HA group according to their willingness and the doctor's advice. The combination group was treated with DQS six times a day and HA four times a day, and the HA group was treated with HA four times a day after FS-LASIK. Ocular surface disease index (OSDI), ocular symptom score, vision-related score, environmental score, tear meniscus height (TMH), first non-invasive tear breakup time (NIBUT-First), average non-invasive tear breakup time (NIBUT-Ave), tear breakup time (TBUT), Schirmer I test (SIT), corneal fluorescein staining score (CFS), bulbar redness score, limbal redness score, lipid layer grade (LLG), meiboscore, lid margin abnormality, corneal sensitivity, and corneal nerve parameters were examined before surgery and at 1 week and 1 month after surgery. Surface regularity index (SRI) was also examined before surgery and at 1 month postoperatively. Results: OSDI score (p = 0.024) and vision-related score (p = 0.026) were significantly lower in the combination group than in the HA group at 1 month after FS-LASIK, especially in patients with preoperative dry eye symptoms. The increasements of CFS (p = 0.018), bulbar redness score (p = 0.021), and limbal redness score (p = 0.009) were significantly lower in the combination group than in the HA group at 1 week after FS-LASIK. But other ocular surface parameters showed no difference between both groups at 1 week and 1 month after FS-LASIK. LLG was significantly higher in the combination group than in the HA group at 1 week (p = 0.004) and 1 month (p < 0.001) after surgery, especially in patients with high meiboscore. Additional DQS significantly improved corneal sensitivity in patients without preoperative dry eye symptoms at 1 month after FS-LASIK (p = 0.041). Conclusion: The combination therapy with DQS and HA significantly relieved subjective symptoms, improved ocular surface status, and had the potential to promote corneal nerve growth in patients after FS-LASIK.

Prediction of Implantable Collamer Lens Vault Based on Preoperative Biometric Factors and Lens Parameters.

PURPOSE: To establish and validate the accuracy of implantable collamer lens (ICL) vault size prediction formula based on preoperative biometric factors and lens parameters. METHODS: This study included 300 patients (300 eyes) with Visian ICL V4c (STAAR Surgical) implantation. They were randomly divided into the formula establishment group and formula validation group. Anterior segment measurements, ICL V4c size and power, and vault 1 week postoperatively were collected from all patients. Multiple linear regression analysis was performed to establish the prediction formula. Mean absolute error (MAE), median absolute error (MedAE), root mean square error (RMSE), and Bland-Altman diagrams were used to evaluate the prediction formula. RESULTS: Anterior chamber depth (ACD) had the greatest influence on vault 1 week after ICL V4c implantation, followed by ICL V4c size and angle-to-angle distance (ATA). The prediction formula was obtained according to the partial regression coefficient, which was vault (mm) = -1.279 + 0.291 × ACD (mm) + 0.210 × ICL V4c size (mm) - 0.144 × ATA (mm) (R2 = 0.661). In the formula validation group, the mean predictive vault, MAE, MedAE, and RMSE were 628.10, 135.09, 130.42, and 150.46 µm, respectively. The Bland-Altman diagram showed the predictive vault was in good agreement with the actual vault. CONCLUSIONS: A novel ICL V4c vault prediction formula was developed and shown to be an effective method for predicting the vault to reduce surgical complications. [J Refract Surg. 2023;39(5):332-339.].

Tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6.

ETHNOPHARMACOLOGICAL RELEVANCE: Xanthium sibiricum Patrin ex Widder (X. sibiricum) are widely used traditional herbal medicines for arthritis treatment in China. Rheumatoid arthritis (RA) is characterized by progressive destructions of joints, which is accompanied by chronic, progressive inflammatory disorder. According to our previous research, tomentosin was isolated from X. sibiricum and revealed anti-inflammatory activity. However, the potential therapeutic effect of tomentosin on RA and the anti-inflammatory mechanism of tomentosin remain to be clarified. The present study lays theoretical support for X. sibiricum in RA treatment, also provides reference for further development of X. sibiricum in clinic. AIM OF THE STUDY: To investigate the effect of tomentosin in collagen-induced arthritis (CIA) mice and reveal its underlying mechanism. MATERIALS AND METHODS: In vivo, tomentosin (10, 20 and 40 mg/kg) was given to CIA mice for seven consecutive days, to evaluate its therapeutic effect and anti-inflammatory activity. In vitro, THP-1-derived macrophages were used to verify the effect of tomentosin on inflammation. Then, molecular docking and experiments in vitro was conducted to predict and explore the mechanism of tomentosin inhibiting inflammation. RESULTS: Tomentosin attenuated the severity of arthritis in CIA mice, which was evidenced by the swelling of the hind paws, arthritis scores, and pathological changes. Particularly, tomentosin effectively reduced the ratio of M1 macrophage and TNF-α levels in vitro and vivo. Then, molecular docking and experiments in vitro was carried out, indicating that tomentosin inhibited M1 polarization and TNF-α levels accompanied by the increase of MERTK and up-regulated GAS6 levels. Moreover, it has been proved that GAS6 was necessary for MERTK activation and tomentosin could up-regulate GAS6 levels effectively in transwell system. Further mechanistic studies revealed that tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6 in transwell system. CONCLUSION: Tomentosin relieved the severity of CIA mice by inhibiting M1 polarization. Furthermore, tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6.

Rapid discrimination of Shigella spp. and Escherichia coli via label-free surface enhanced Raman spectroscopy coupled with machine learning algorithms.

Shigella and enterotoxigenic Escherichia coli (ETEC) are major bacterial pathogens of diarrheal disease that is the second leading cause of childhood mortality globally. Currently, it is well known that Shigella spp., and E. coli are very closely related with many common characteristics. Evolutionarily speaking, Shigella spp., are positioned within the phylogenetic tree of E. coli. Therefore, discrimination of Shigella spp., from E. coli is very difficult. Many methods have been developed with the aim of differentiating the two species, which include but not limited to biochemical tests, nucleic acids amplification, and mass spectrometry, etc. However, these methods suffer from high false positive rates and complicated operation procedures, which requires the development of novel methods for accurate and rapid identification of Shigella spp., and E. coli. As a low-cost and non-invasive method, surface enhanced Raman spectroscopy (SERS) is currently under intensive study for its diagnostic potential in bacterial pathogens, which is worthy of further investigation for its application in bacterial discrimination. In this study, we focused on clinically isolated E. coli strains and Shigella species (spp.), that is, S. dysenteriae, S. boydii, S. flexneri, and S. sonnei, based on which SERS spectra were generated and characteristic peaks for Shigella spp., and E. coli were identified, revealing unique molecular components in the two bacterial groups. Further comparative analysis of machine learning algorithms showed that, the Convolutional Neural Network (CNN) achieved the best performance and robustness in bacterial discrimination capacity when compared with Random Forest (RF) and Support Vector Machine (SVM) algorithms. Taken together, this study confirmed that SERS paired with machine learning could achieve high accuracy in discriminating Shigella spp., from E. coli, which facilitated its application potential for diarrheal prevention and control in clinical settings. Graphical abstract.

Targeting acetyl-CoA carboxylase 1 for cancer therapy.

Metabolic adaptation is an emerging hallmark of tumors. De novo fatty acid synthesis is an important metabolic process to produce metabolic intermediates for energy storage, biosynthesis of membrane lipids and generation of signaling molecules. Acetyl-CoA carboxylase 1 (ACC1) is a critical enzyme in the fatty acid synthesis, which carboxylates acetyl-CoA carboxylic acid to form malonyl-CoA. The role of acetyl-CoA carboxylase 1 in fatty acid synthesis makes it a promising therapeutic target for various metabolic diseases such as non-alcoholic fatty liver disease, obesity and diabetes. Tumors have a high energy flow and a strong dependence on fatty acid synthesis. Thus, acetyl-CoA carboxylase inhibition has become a potential choice for anti-tumor therapy. In this review, we first introduced the structure and expression pattern of Acetyl-CoA carboxylase 1. We also discussed the molecular mechanisms of acetyl-CoA carboxylase 1 in the initiation and progression of various cancer types. Furthermore, acetyl-CoA carboxylase1 inhibitors has also been discussed. Collectively, we summarized the interplay between acetyl-CoA carboxylase 1 and tumorigenesis, indicating acetyl-CoA carboxylase 1 as a promising therapeutic target for tumor management.

Regio- and chemoselective hydroamination of unactivated alkenes with anthranils via NiH-catalysis.

A NiH-catalyzed polarity-reversed hydroamination of ß,γ-, γ,δ- and δ,ε-unsaturated alkenes with electrophilic anthranils was developed. This reaction proceeds in a highly regio- and chemoselective manner to afford γ, δ and ε-arylamines bearing a carbonyl or alcohol functionality with 100% atom efficiency. Preliminary mechanistic studies indicate that the chemoselectivity is controlled by the base and the alcohol product is derived from the base-catalyzed hydrosilylation of the CO bond.

Panax notoginseng saponins (PNS) attenuate Th17 cell differentiation in CIA mice via inhibition of nuclear PKM2-mediated STAT3 phosphorylation.

CONTEXT: Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. Panax notoginseng (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation. OBJECTIVE: To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2). MATERIALS AND METHODS: Naive CD4+T cells were treated with IL-6, IL-23 and TGF-ß to induce Th17 cell differentiation. Apart from the Control group, other cells were treated with PNS (5, 10, 20 µg/mL). After the treatment, Th17 cell differentiation, PKM2 expression, and STAT3 phosphorylation were measured via flow cytometry, western blots, or immunofluorescence. PKM2-specific allosteric activator (Tepp-46, 50, 100, 150 µM) and inhibitor (SAICAR, 2, 4, 8 µM) were used to verify the mechanisms. A CIA mouse model was established and divided into control, model, and PNS (100 mg/kg) groups to assess an anti-arthritis effect, Th17 cell differentiation, and PKM2/STAT3 expression. RESULTS: PKM2 expression, dimerization, and nuclear accumulation were upregulated upon Th17 cell differentiation. PNS inhibited the Th17 cells, RORγt expression, IL-17A levels, PKM2 dimerization, and nuclear accumulation and Y705-STAT3 phosphorylation in Th17 cells. Using Tepp-46 (100 µM) and SAICAR (4 µM), we demonstrated that PNS (10 µg/mL) inhibited STAT3 phosphorylation and Th17 cell differentiation by suppressing nuclear PKM2 accumulation. In CIA mice, PNS attenuated CIA symptoms, reduced the number of splenic Th17 cells and nuclear PKM2/STAT3 signaling. DISCUSSION AND CONCLUSIONS: PNS inhibited Th17 cell differentiation through the inhibition of nuclear PKM2-mediated STAT3 phosphorylation. PNS may be useful for treating RA.

Mechanism of piR-1245/PIWI-like protein-2 regulating Janus kinase-2/signal transducer and activator of transcription-3/vascular endothelial growth factor signaling pathway in retinal neovascularization.

Inhibiting retinal neovascularization is the optimal strategy for the treatment of retina-related diseases, but there is currently no effective treatment for retinal neovascularization. P-element-induced wimpy testis (PIWI)-interacting RNA (piRNA) is a type of small non-coding RNA implicated in a variety of diseases. In this study, we found that the expression of piR-1245 and the interacting protein PIWIL2 were remarkably increased in human retinal endothelial cells cultured in a hypoxic environment, and cell apoptosis, migration, tube formation and proliferation were remarkably enhanced in these cells. Knocking down piR-1245 inhibited the above phenomena. After intervention by a p-JAK2 activator, piR-1245 decreased the expression of hypoxia inducible factor-1α and vascular endothelial growth factor through the JAK2/STAT3 pathway. For in vivo analysis, 7-day-old newborn mice were raised in 75 ± 2% hyperoxia for 5 days and then piR-1245 in the retina was knocked down. In these mice, the number of newly formed vessels in the retina was decreased, the expressions of inflammation-related proteins were reduced, the number of apoptotic cells in the retina was decreased, the JAK2/STAT3 pathway was inhibited, and the expressions of hypoxia inducible factor-1α and vascular endothelial growth factor were decreased. Injection of the JAK2 inhibitor JAK2/TYK2-IN-1 into the vitreous cavity inhibited retinal neovascularization in mice and reduced expression of hypoxia inducible factor-1α and vascular endothelial growth factor. These findings suggest that piR-1245 activates the JAK2/STAT3 pathway, regulates the expression of hypoxia inducible factor-1α and vascular endothelial growth factor, and promotes retinal neovascularization. Therefore, piR-1245 may be a new therapeutic target for retinal neovascularization.