Key points for protecting the external branch of the superior laryngeal nerve in open thyroidectomy: A possible exploration technique.

OBJECTIVE: Injury of the external branch of the superior laryngeal nerve (EBSLN) is easily overlooked in thyroidectomy, and voice changes caused by the injury have a negative effect on an increasing number of patients. This study aimed to reduce the injury rate of EBSLN by expanding the sternothyroid-laryngeal triangle and standardizing the exploration procedure. METHODS: A total of 520 patients who had undergone thyroidectomy at the First Affiliated Hospital of Nanchang University between September 2021 and April 2022 were analyzed. During the operation, the exposure rate of the EBSLN before and after sternothyroid-laryngeal triangle expansion was compared, and all EBSLNs were anatomically classified. RESULTS: The exposure rate of EBSLN after sternothyroid-laryngeal triangle expansion reached 82.7%, which is much higher than that before sternothyroid-laryngeal triangle expansion (33.7%), and voice change caused by injury of the EBSLN was reported in one case (the injury rate was 0.2%). The classification and proportion of the EBSLN were as follows: Type 1 (55.3%), the nerve ran within 1 cm above the STP, but no coincidence or crossover with blood vessels was observed in this region; Type 2 (14.7%), the nerve travelled within 1 cm above the STP and overlapped or intersected with blood vessels in this region; Type 3 (12.7%), the EBSLN ran below the level of the STP; and Type 4 (17.3%), no EBSLN was observed within 1 cm above the STP. CONCLUSION: In thyroidectomy, injury to the EBSLN can be effectively reduced by expanding the sternothyroid-laryngeal triangle and exploring the upper pole area of the thyroid as far as possible, which has great clinical significance in reducing postoperative voice box injury.

GPX4 inhibits apoptosis of thyroid cancer cells through regulating the FKBP8/Bcl-2 axis.

GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in cell apoptosis is rarely reported, and its role in apoptosis of thyroid cancer (TC) cell has not been reported. The analysis of TCGA database showed that both GPX4 and FKBP8 were highly expressed in TC tumor tissues; The expression of GPX4 and FKBP8 were positively correlated. The immunohistochemical analysis further confirmed that GPX4 and FKBP8 were highly expressed in TC tumor tissues. In addition, the high expression of GPX4 and FKBP8 were both significantly correlated with the poor prognosis of TC. Silencing GPX4 significantly inhibited the proliferation, induced apoptosis of TC cells, and reduced tumor growth in mice. The co-immunoprecipitation assay revealed a physical interaction between GPX4 and FKBP8 observed in the TC cells. Knockdown of FKBP8 significantly inhibited the proliferation and induced apoptosis of TC cells. Rescue experiments suggested that knockdown of FKBP8 could reverse the strengthens of cell proliferation and apoptosis and the higher expression of FKBP8 and Bcl-2 caused by overexpression of GPX4. Our results suggest that the GPX4/FKBP8/Bcl-2 axis promotes TC development by inhibiting TC cell apoptosis, which provides potential molecular targets for TC therapeutic strategies.

Ultrasound image-based deep learning to assist in diagnosing gross extrathyroidal extension thyroid cancer: a retrospective multicenter study.

Background: The presence of gross extrathyroidal extension (ETE) in thyroid cancer will affect the prognosis of patients, but imaging examination cannot provide a reliable diagnosis for it. This study was conducted to develop a deep learning (DL) model for localization and evaluation of thyroid cancer nodules in ultrasound images before surgery for the presence of gross ETE. Methods: From January 2016 to December 2021 grayscale ultrasound images of 806 thyroid cancer nodules (4451 images) from 4 medical centers were retrospectively analyzed, including 517 no gross ETE nodules and 289 gross ETE nodules. 283 no gross ETE nodules and 158 gross ETE nodules were randomly selected from the internal dataset to form a training set and validation set (2914 images), and a multitask DL model was constructed for diagnosing gross ETE. In addition, the clinical model and the clinical and DL combined model were constructed. In the internal test set [974 images (139 no gross ETE nodules and 83 gross ETE nodules)] and the external test set [563 images (95 no gross ETE nodules and 48 gross ETE nodules)], the diagnostic performance of DL model was verified based on the pathological results. And then, compared the results with the diagnosis by 2 senior and 2 junior radiologists. Findings: In the internal test set, DL model demonstrated the highest AUC (0.91; 95% CI: 0.87, 0.96), which was significantly higher than that of two senior radiologists [(AUC, 0.78; 95% CI: 0.71, 0.85; P < 0.001) and (AUC, 0.76; 95% CI: 0.70, 0.83; P < 0.001)] and two juniors radiologists [(AUC, 0.65; 95% CI: 0.58, 0.73; P < 0.001) and (AUC, 0.69; 95% CI: 0.62, 0.77; P < 0.001)]. DL model was significantly higher than clinical model [(AUC, 0.84; 95% CI: 0.79, 0.89; P = 0.019)], but there was no significant difference between DL model and clinical and DL combined model [(AUC, 0.94; 95% CI: 0.91, 0.97; P = 0.143)]. In the external test set, DL model also demonstrated the highest AUC (0.88, 95% CI: 0.81, 0.94), which was significantly higher than that of one of senior radiologists [(AUC, 0.75; 95% CI: 0.66, 0.84; P = 0.008) and (AUC, 0.81; 95% CI: 0.72, 0.89; P = 0.152)] and two junior radiologists [(AUC, 0.72; 95% CI: 0.62, 0.81; P = 0.002) and (AUC, 0.67; 95 CI: 0.57, 0.77; P < 0.001]. There was no significant difference between DL model and clinical model [(AUC, 0.85; 95% CI: 0.79, 0.91; P = 0.516)] and clinical + DL model [(AUC, 0.92; 95% CI: 0.87, 0.96; P = 0.093)]. Using DL model, the diagnostic ability of two junior radiologists was significantly improved. Interpretation: The DL model based on ultrasound imaging is a simple and helpful tool for preoperative diagnosis of gross ETE thyroid cancer, and its diagnostic performance is equivalent to or even better than that of senior radiologists. Funding: Jiangxi Provincial Natural Science Foundation (20224BAB216079), the Key Research and Development Program of Jiangxi Province (20181BBG70031), and the Interdisciplinary Innovation Fund of Natural Science, Nanchang University (9167-28220007-YB2110).

Disproportionation-Inspired Construction of Highly Functionalized Bicyclo[3.2.1]octanes.

The formation of one unavoidable byproduct in traditional disproportionation reactions limits their applications in synthesis. Inspired by convergent disproportionation, we develop an iodine-induced cyclization and oxidation of allylic alcohols to produce highly functionalized bicyclo[3.2.1]octanes through creation of six new bonds. Guided by the mechanism, we elaborated a variety of other bicyclo[3.2.1]octanes bearing distinct groups with presynthesized dienes and enones as the starting materials. This work provides a divergent access to bicyclo[3.2.1]octane frameworks.

Application of Artificial Intelligence in Measuring Novel pH-Impedance Metrics for Optimal Diagnosis of GERD.

Novel metrics extracted from pH-impedance monitoring can augment the diagnosis of gastroesophageal reflux disease (GERD). Artificial intelligence (AI) is being widely used to improve the diagnostic capabilities of various diseases. In this review, we update the current literature regarding applications of artificial intelligence in measuring novel pH-impedance metrics. AI demonstrates high performance in the measurement of impedance metrics, including numbers of reflux episodes and post-reflux swallow-induced peristaltic wave index and, furthermore, extracts baseline impedance from the entire pH-impedance study. AI is expected to play a reliable role in facilitating measuring novel impedance metrics in patients with GERD in the near future.

Artificial intelligence facilitates measuring reflux episodes and postreflux swallow-induced peristaltic wave index from impedance-pH studies in patients with reflux disease.

BACKGROUND/AIM: Reflux episodes and postreflux swallow-induced peristaltic wave (PSPW) index are useful impedance parameters that can augment the diagnosis of gastroesophageal reflux disease (GERD). However, manual analysis of pH-impedance tracings is time consuming, resulting in limited use of these novel impedance metrics. This study aims to evaluate whether a supervised learning artificial intelligence (AI) model is useful to identify reflux episodes and PSPW index. METHODS: Consecutive patients underwent 24-h impedance-pH monitoring were enrolled for analysis. Multiple AI and machine learning with a deep residual net model for image recognition were explored based on manual interpretation of reflux episodes and PSPW according to criteria from the Wingate Consensus. Intraclass correlation coefficients (ICCs) were used to measure the strength of inter-rater agreement of data between manual and AI interpretations. RESULTS: We analyzed 106 eligible patients with 7939 impedance events, of whom 38 patients with pathological acid exposure time (AET) and 68 patients with physiological AET. On the manual interpretation, patients with pathological AET had more reflux episodes and lower PSPW index than those with physiological AET. Overall accuracy of AI identification for reflux episodes and PSPW achieved 87% and 82%, respectively. Inter-rater agreements between AI and manual interpretations achieved excellent for individual numbers of reflux episodes and PSPW index (ICC = 0.965 and ICC = 0.921). CONCLUSIONS: AI has the potential to accurately and efficiently measure impedance metrics including reflux episodes and PSPW index. AI can be a reliable adjunct for measuring novel impedance metrics for GERD in the near future.

Skeleton-Reorganizing Coupling Reactions of Cycloheptatriene and Cycloalkenones with Amines.

Skeletal reorganization reactions have emerged as an intriguing tool for converting readily available compounds into complicated molecules inaccessible by traditional methods. Herein, we report a unique skeleton-reorganizing coupling reaction of cycloheptatriene and cycloalkenones with amines. In the presence of Rh/acid catalysis, cycloheptatriene can selectively couple with anilines to deliver fused 1,2-dihydroquinoline products. Mechanistic studies indicate that the retro-Mannich type ring-opening and subsequent intramolecular Povarov reaction account for the ring reorganization. Our mechanistic studies also revealed that skeleton-reorganizing amination between anilines and cycloalkenones can be achieved with acid. The synthetic utilization of this skeleton-reorganizing coupling reaction was showcased with a gram-scale reaction, synthetic derivatizations, and the late-stage modification of commercial drugs.

Xuesaitong Combined with Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats by Activating Keap1/Nrf2 Signaling and Mitophagy in Hippocampal Tissue.

Ischemic stroke is the most common type of cerebrovascular disease with high mortality and poor prognosis, and cerebral ischemia-reperfusion (CI/R) injury is the main murderer. Here, we attempted to explore the effects and mechanism of Xuesaitong (XST) combined with dexmedetomidine (Dex) on CI/R injury in rats. First, a rat model of CI/R injury was constructed via the middle cerebral artery occlusion (MCAO) method and treated with XST and Dex alone or in combination. Then, on the 5th and 10th days of treatment, the neurological impairment was assessed using the modified neurological severity scores (mNSS), the 8-arm radial maze test (8ARMT), novel object recognition test (NORT), and fear conditioning test (FCT). H&E staining was performed to observe the pathological changes of the hippocampus. ELISA and related kits were used to assess the monoamine neurotransmitters and antioxidant enzyme activities in the hippocampus. The ATP, mitochondrial membrane potential levels, and qRT-PCR of genes related to mitochondrial function were determined to assess mitochondrial functions in the hippocampus and western blot to determine Keap1/Nrf2 signaling pathway and mitophagy-related protein expression. The results showed that XST combined with Dex significantly reduced mNSS, improved spatial memory and learning deficits, and enhanced fear memory and cognitive memory ability in CI/R rats, which was superior to single-drug treatment. Moreover, XST combined with Dex treatment improved hippocampal histopathological damage; significantly increased the levels of monoamine neurotransmitters, neurotrophic factors, ATP, and mitochondrial membrane potential; and upregulated the activities of antioxidant enzymes and the expression of mitophagy-related proteins in the hippocampus of CI/R rats. XST combined with Dex treatment also activated the Keap1/Nrf2 signaling and upregulated the protein expression of downstream antioxidant enzymes HO-1 and NQ. Altogether, this study showed that a combination of XST and Dex could activate the Keap1/Nrf2 signaling and mitophagy to protect rats from CI/R-related neurological impairment.

Investigation of Factors Influencing the Fear of Cancer Recurrence in Breast Cancer Patients Using Structural Equation Modeling: A Cross-Sectional Study.

Objective: This study aimed to investigate the fear of cancer recurrence (FCR) in breast cancer patients and develop a structural equation model of influencing factors to help formulate clinical intervention strategies. Methods: A convenience sample of 325 patients was surveyed using a general and disease-related data questionnaire, which combined the Fear of Progression Questionnaire-Short Form, Mishel Uncertainty in Illness Scale, Perceived Social Support Scale, and Medical Coping Modes Questionnaire. Results: The total score of FCR in breast cancer patients was 35.06 ± 10.83, and 53.8% of patients reached the clinical level. The structural equation model demonstrated that illness uncertainty had a direct positive impact on FCR (ß = 0.275, p < 0.05), and it could have an indirect impact through social support and resignation coping methods (ß = 0.254, p < 0.05). Conclusion: The fear of cancer recurrence in breast cancer patients needs further understanding. Medical staff can reduce or buffer FCR in breast cancer patients by strengthening positive influences, such as social support, or weakening negative influences, such as illness uncertainty and resignation coping.

Selective C-S Bond Constructions Using Inorganic Sulfurs via Photoinduced Electron Donor-Acceptor Activation.

By complementing traditional transition metal catalysis, photoinduced catalysis has emerged as a versatile and sustainable way to achieve carbon-heteroatom bond formation. This work discloses a visible-light-induced reaction for the formation of a C-S bond from aryl halides and inorganic sulfuration agents via electron donor-acceptor (EDA) complex photocatalysis. Divergent formations of organic sulfide and disulfide have been demonstrated under mild conditions. Preliminary mechanistic studies suggest that visible-light-induced intracomplex charge transfer within the monosulfide-anion-containing EDA complex permits the C-S bond construction reactivity.

Rhodium-Catalyzed Deuterated Tsuji-Wilkinson Decarbonylation of Aldehydes with Deuterium Oxide.

The recent surge in the applications of deuterated drug candidates has rendered an urgent need for diverse deuterium labeling techniques. Herein, an efficient Rh-catalyzed deuterated Tsuji-Wilkinson decarbonylation of naturally available aldehydes with D2O is developed. In this reaction, D2O not only acts as a deuterated reagent and solvent but also promotes Rh-catalyzed decarbonylation. In addition, decarbonylative strategies for the synthesis of terminal monodeuterated alkenes from α,ß-unsaturated aldehydes are within reach.

Electrochemically driven regioselective C-H phosphorylation of group 8 metallocenes.

Metallocenes are privileged backbones for synthesis and catalysis. However, the direct dehydrogenative C-H functionalization of unsymmetric metallocenes suffers from reactivity and selectivity issues. Herein, we report an electrochemically driven regioselective C-H phosphorylation of group 8 metallocenes. Mechanistic investigations indicate this dehydrogenative cross coupling occurs through an electrophilic radical substitution of the metallocene with a phosphoryl radical, facilitated by the metallocene itself. This work not only offers an efficient and divergent synthesis of phosphorylated metallocenes, but also provides a guide to interpret the reactivity and regioselectivity for the C-H functionalization of unsymmetric metallocenes.

Artificial Neural Network-Based Ultrasound Radiomics Can Predict Large-Volume Lymph Node Metastasis in Clinical N0 Papillary Thyroid Carcinoma Patients.

Objective: To evaluate the ability of artificial neural network- (ANN-) based ultrasound radiomics to predict large-volume lymph node metastasis (LNM) preoperatively in clinical N0 disease (cN0) papillary thyroid carcinoma (PTC) patients. Methods: From January 2020 to April 2021, 306 cN0 PTC patients admitted to our hospital were retrospectively reviewed and divided into a training (n = 183) cohort and a validation cohort (n = 123) in a 6 : 4 ratio. Radiomic features quantitatively extracted from ultrasound images were pruned to train one ANN-based radiomic model and three conventional machine learning-based classifiers in the training cohort. Furthermore, an integrated model using ANN was constructed for better prediction. Meanwhile, the prediction of the two models was evaluated in the papillary thyroid microcarcinoma (PTMC) and conventional papillary thyroid cancer (CPTC) subgroups. Results: The radiomic model showed better discrimination than other classifiers for large-volume LNM in the validation cohort, with an area under the receiver operating characteristic curve (AUROC) of 0.856 and an area under the precision-recall curve (AUPR) of 0.381. The performance of the integrated model was better, with an AUROC of 0.910 and an AUPR of 0.463. According to the calibration curve and decision curve analysis, the radiomic and integrated models had good calibration and clinical usefulness. Moreover, the models had good predictive performance in the PTMC and CPTC subgroups. Conclusion: ANN-based ultrasound radiomics could be a potential tool to predict large-volume LNM preoperatively in cN0 PTC patients.

Schistosoma japonicum infection associated with membranous nephropathy: a case report.

BACKGROUND: Schistosomiasis is one of the most contagious parasitic diseases affecting humans; however, glomerular injury is a rare complication mainly described with Schistosoma mansoni infection. We report a case of membranous nephropathy associated with Schistosoma japonicum infection in a Chinese man. CASE PRESENTATION: A 51-year-old Chinese male with a long history of S. japonicum infection presented to the hospital with a slowly progressing severe lower limb edema and foaming urine for over 5 months. Serum S. japonicumantigen test was positive and immunohistochemistry showed that the glomeruli were positive for the antigens. The renal pathologic diagnosis was stage III membranous nephropathy. The patient was treated with glucocorticoid, praziquantel, and an angiotensin-converting enzyme inhibitor. The edema in both lower limbs disappeared within 2 weeks, but his renal function declined progressively and proteinuria persisted after 5 months of therapy. CONCLUSIONS: Different classes of schistosomal glomerulopathy have completely different clinical manifestation and prognosis. Therefore, efforts should focus on alleviating symptoms, prevention, and early detection. S. japonicumassociated with membranous nephropathy may show a good curative effect and prognosis. However, it is necessary to monitor the renal function in such patients.

Near infrared spectroscopy assessed oxygenated hemoglobin with sleep quality among college students / 中国学校卫生

Objective@#Functional near infrared spectroscopy (fNIRS) was used to assess brain oxygenated hemoglobin (Oxy Hb) activation in college students with different sleep quality under the verbal fluency task (VFT), so as to better provide a theoretical basis for the neural mechanism for sleep quality improvement of college students.@*Methods@#A simple random sampling method was used to investigate 96 college students from one university during 2020 and 2021. According to the results of the Pittsburgh Sleep Quality Index(PSQI), participants were divided into 3 groups: good sleep quality group( n =45), moderate group( n =33), and poor group( n =18). The 53 channel near infrared spectroscopy to collect cerebral blood oxygen signals under the VFT task. Association between oxygenated hemoglobin with sleep quality was analyzed.@*Results@#About 18.75% of college students reported sleep quality problems, including long sleep latency (0.97±0.97) and poor subjective sleep quality (0.96±0.72). There was a significant negative correlation between PSQI score and average oxygenated hemoglobin (Avg HbO) index of dorsolateral prefrontal lobe ( r =-0.23, P =0.03). The Avg HbO index differed significantly between good and poor sleep quality groups on dorsolateral prefrontal lobe( P =0.05).@*Conclusion@#This study verified that there is a positive correlation between sleep quality and cognitive ability among college students. The fNIRS technique could accurately collect blood oxygen signals from dorsolateral prefrontal lobe during cognitive tasks, which proves to be an effective tool for identifying sleep quality of college students.

Construction of a potent pan-vaccine based on the evolutionary tendency of SARS-CoV-2 spike protein.

SARS-CoV-2 continued to spread globally along with different variants. Here, we systemically analyzed viral infectivity and immune-resistance of SARS-CoV-2 variants to explore the underlying rationale of viral mutagenesis. We found that the Beta variant harbors both high infectivity and strong immune resistance, while the Delta variant is the most infectious with only a mild immune-escape ability. Remarkably, the Omicron variant is even more immune-resistant than the Beta variant, but its infectivity increases only in Vero E6 cells implying a probable preference for the endocytic pathway. A comprehensive analysis revealed that SARS-CoV-2 spike protein evolved into distinct evolutionary paths of either high infectivity plus low immune resistance or low infectivity plus high immune resistance, resulting in a narrow spectrum of the current single-strain vaccine. In light of these findings and the phylogenetic analysis of 2674 SARS-CoV-2 S-protein sequences, we generated a consensus antigen (S6) taking the most frequent mutations as a pan-vaccine against heterogeneous variants. As compared to the ancestry SWT vaccine with significantly declined neutralizations to emerging variants, the S6 vaccine elicits broadly neutralizing antibodies and full protections to a wide range of variants. Our work highlights the importance and feasibility of a universal vaccine strategy to fight against antigen drift of SARS-CoV-2.

Nomogram Combining Radiomics With the American College of Radiology Thyroid Imaging Reporting and Data System Can Improve Predictive Performance for Malignant Thyroid Nodules.

PURPOSE: To develop and validate a nomogram combining radiomics of B-mode ultrasound (BMUS) images and the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) for predicting malignant thyroid nodules and improving the performance of the guideline. METHOD: A total of 451 thyroid nodules referred for surgery and proven pathologically at an academic referral center from January 2019 to September 2020 were retrospectively collected and randomly assigned to training and validation cohorts (7:3 ratio). A nomogram was developed through combining the BMUS radiomics score (Rad-Score) with ACR TI-RADS score (ACR-Score) in the training cohort; the performance of the nomogram was assessed with respect to discrimination, calibration, and clinical application in the validation and entire cohorts. RESULTS: The ACR-Rad nomogram showed good calibration and yielded an AUC of 0.877 (95% CI 0.836-0.919) in the training cohort and 0.864 (95% CI 0.799-0.931) in the validation cohort, which were significantly better than the ACR-Score model (p < 0.001 and 0.031, respectively). The significantly improved AUC, net reclassification index (NRI), and integrated discriminatory improvement (IDI) of the nomogram were found for both senior and junior radiologists (all p < 0.001). Decision curve analysis indicated that the nomogram was clinically useful. When cutoff values for 50% predicted malignancy risk (ACR-Rad_50%) were applied, the nomogram showed increased specificity, accuracy and positive predictive value (PPV), and decreased unnecessary fine-needle aspiration (FNA) rates in comparison to ACR TI-RADS. CONCLUSION: The ACR-Rad nomogram has favorable value in predicting malignant thyroid nodules and improving performance of the ACR TI-RADS for senior and junior radiologists.

Photo-induced catalytic halopyridylation of alkenes.

The Mizoroki-Heck reaction and its reductive analogue are staples of organic synthesis, but the ensuing products often lack a chemical handle for further transformation. Here we report an atom-economical cross-coupling of halopyridines and unactivated alkenes under photoredox catalysis to afford a series of alkene halopyridylation products. This protocol with mild and redox neutral conditions contributes broad substrate scope. As a complement to conventional Heck-type reaction, this radical process avoids the involvement of ß-H elimination and thus useful pyridyl and halide groups could be simultaneously and regioselectively incorporated onto alkenes. The success depends on TFA-promoted domino photocatalytic oxidative quenching activation and radical-polar crossover pathway. Plausible mechanism is proposed based on mechanistic investigations. Moreover, the reserved C - X bonds of these products are beneficial for performing further synthetic elaborations.

Comparison of Clinical Efficacy and Safety of Metformin Sustained-Release Tablet (II) (Dulening) and Metformin Tablet (Glucophage) in Treatment of Type 2 Diabetes Mellitus.

Objectives: This study investigated the clinical efficacy and safety of metformin hydrochloride sustained-release (SR) tablet (II) produced by Dulening and the original metformin hydrochloride tablet produced by Glucophage in the treatment of type 2 diabetes mellitus (T2DM). Methods: This randomized, open and parallel controlled clinical trial consecutively recruited a total of 886 patients with T2DM in 40 clinical centers between May 2016 and December 2018. These patients were randomly assigned to the Dulening group (n=446), in which patients were treated with Dulening metformin SR tablets, and the Glucophage group (n=440), in which patients were treated with Glucophage metformin tablets, for 16 weeks. The changes in the levels of glycated hemoglobin (HbAc1) and fasting blood glucose (FBG) as well as weight loss were compared between these two groups. Also, the overall incidence of adverse drug reactions (ADRs) and the incidence of ADR of the gastrointestinal system observed in patients of these two groups were also compared. Results: There were no significant differences in demographic and basal clinical characteristics between these two groups. The Dulening and Glucophage groups showed comparable levels of decrease in HbA1c levels, FBG and weight loss after 12-week treatment (all p>0.05). The Dulening group had a significantly lower overall incidence of ADRs as well as gastrointestinal ADR than the Glucophage group. Conclusions: Metformin SR tablets (II) and the original metformin tablets exhibit similar therapeutic efficacy in the treatment of T2DM, but metformin SR tablets (II) has the significantly lower incidence of ADRs than the original metformin tablets.

The serendipitous effect of KF in Ritter reaction: Photo-induced amino-alkylation of alkenes.

Ritter reaction has been recognized as an elegant strategy to construct the C-N bond. Its key feature is forming the carbocation for nucleophilic attack by nitriles. Herein, we report a complementary visible-light-induced three-component Ritter reaction of alkenes, nitriles, and α-bromo nitriles/esters, thereby providing mild and rapid access to various γ-amino nitriles/acids. Mechanistic studies indicated that traceless fluoride relay, transforming KF into imidoyl fluoride intermediate, is critical for the efficient reaction switch from atom transfer radical addition (ATRA) to the Ritter reaction. This approach to amino-alkylation of alkenes is chemoselective and operationally simple.