Integrated transcriptomic and metabolomic analyses reveals anthocyanin biosynthesis in leaf coloration of quinoa (Chenopodium quinoa Willd.).

BACKGROUND: Quinoa leaves demonstrate a diverse array of colors, offering a potential enhancement to landscape aesthetics and the development of leisure-oriented sightseeing agriculture in semi-arid regions. This study utilized integrated transcriptomic and metabolomic analyses to investigate the mechanisms underlying anthocyanin synthesis in both emerald green and pink quinoa leaves. RESULTS: Integrated transcriptomic and metabolomic analyses indicated that both flavonoid biosynthesis pathway (ko00941) and anthocyanin biosynthesis pathway (ko00942) were significantly associated with anthocyanin biosynthesis. Differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were analyzed between the two germplasms during different developmental periods. Ten DEGs were verified using qRT-PCR, and the results were consistent with those of the transcriptomic sequencing. The elevated expression of phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), 4-coumarate CoA ligase (4CL) and Hydroxycinnamoyltransferase (HCT), as well as the reduced expression of flavanone 3-hydroxylase (F3H) and Flavonol synthase (FLS), likely cause pink leaf formation. In addition, bHLH14, WRKY46, and TGA indirectly affected the activities of CHS and 4CL, collectively regulating the levels of cyanidin 3-O-(3'', 6''-O-dimalonyl) glucoside and naringenin. The diminished expression of PAL, 4CL, and HCT decreased the formation of cyanidin-3-O-(6"-O-malonyl-2"-O-glucuronyl) glucoside, leading to the emergence of emerald green leaves. Moreover, the lowered expression of TGA and WRKY46 indirectly regulated 4CL activity, serving as another important factor in maintaining the emerald green hue in leaves N1, N2, and N3. CONCLUSION: These findings establish a foundation for elucidating the molecular regulatory mechanisms governing anthocyanin biosynthesis in quinoa leaves, and also provide some theoretical basis for the development of leisure and sightseeing agriculture.

Catalytic Asymmetric Synthesis of Atropisomers Featuring an Aza Axis.

ConspectusAtropisomers bearing a rotation-restricted axis are common structural units in natural products, chiral ligands, and drugs; thus, the prevalence of asymmetric synthesis has increased in recent decades. Research into atropisomers featuring an N-containing axis (N-X atropisomers) remains in its infancy compared with the well-developed C-C atropisomer analogue. Notably, N-X atropisomers could offer divergent scaffolds, which are extremely important in bioactive molecules. The asymmetric synthesis of N-X atropisomers is recognized as both appealing and challenging. Recently, we devoted our efforts to the catalytic asymmetric synthesis of N-X atropisomers, benzimidazole-aryl N-C atropisomers, indole-aryl N-C atropisomers, hydrogen-bond-assisted N-C atropisomers, pyrrole-pyrrole N-N atropisomers, pyrrole-indole N-N atropisomers, and indole-indole N-N atropisomers. To obtain the N-C atropisomers, an asymmetric Buchwald-Hartwig reaction of amidines or enamines was employed. Using a Pd(OAc)2/(S)-BINAP or Pd(OAc)2/(S)-Xyl-BINAP catalyst system, benzimidazole-aryl N-C atropisomers and indole-aryl N-C atropisomers were readily obtained. To address the issue of the reduced stability of the diarylamine axis, a six-membered intramolecular N-H-O hydrogen bond was introduced into the N-C atropisomer scaffold. A tandem N-arylation/oxidation process was used for the chiral phosphoric acid (CPA)-catalyzed asymmetric synthesis of N-aryl quinone atropisomers. For N-N atropisomers, a copper-mediated asymmetric Friedel-Crafts alkylation/arylation reaction was developed. The desymmetrization process was completed successfully via a Cu(OTf)2/chiral bisoxazoline or (CuOTf)·Tol/bis(phosphine) dioxide system, thereby achieving the first catalytic asymmetric synthesis of N/N bipyrrole atropisomers. Asymmetric Buchwald-Hartwig amination of enamines was utilized to provide N-N bisindole atropisomers with excellent stereogenic control. This was the first asymmetric synthesis of N-N atropisomers featuring a bisindole structural scaffold using the de novo indole construction strategy. The asymmetric N-N heterobiaryl atropisomer synthesis was substantially facilitated using palladium-catalyzed transient directing group (TDG)-mediated C-H functionalization. Atropisomeric alkenylation, allylation, or alkynylation was accomplished using the Pd(OAc)2/l-tert-leucine system. Herein, we summarize our work on the palladium-, copper-, and CPA-catalyzed asymmetric syntheses of N-C and N-N atropisomers. Furthermore, the application of our work in the synthesis of bioactive molecule analogues and axially chiral ligands is demonstrated. Subsequently, the stability of the chiral N-containing axis is briefly discussed in terms of single crystals and obtained rotational barriers. Finally, an outlook on the asymmetric N-X atropisomer synthesis is provided.

Analysis of joint protein expression profile in anterior disc displacement of TMJ with or without OA.

OBJECTIVE: Anterior disc displacement (ADD) is a common clinical issue and may cause osteoarthritis (OA). However, the research of protein changes in synovial fluid as disease development marker and potential treatment clue is still insufficient. MATERIALS AND METHODS: We conducted the high-resolution mass spectrometry (MS) of synovial fluid collected from 60 patients with normal disk position to ADD and ADD with osteoarthritis (OA). The proteins with significant changes among the 3 groups were analyzed by biological information and further validated by in primary rat condyle chondrocytes and OA animal model. RESULTS: FGL2, THBS4, TNC, FN1, OMD etc. were significantly increased in ADD without OA (p < 0.05), which reflected the active extracellular matrix and collagen metabolism. FGFR1, FBLN2, GRB2 etc. were significantly increased in ADD with OA group (p < 0.05), which revealed an association with apoptosis and ferroptosis. Proteins such as P4HB, CBLN4, FHL1, VIM continuously increase in the whole disease progress (p < 0.05). Both the in vitro and in vivo results are consistent with protein changes detected in MS profile. CONCLUSION: This study firstly provides the expression changes of proteins from normal disc condyle relationship toward ADD with OA, which can be selected and studied further as disease progress marker and potential treatment targets.

Analysis of the effect on costochondral graft for TMJ ankylosis with jaw deformities in pediatrics.

OBJECTIVES: To evaluate the effects of costochondral grafting (CCG) used for temporomandibular joint ankylosis (TMJA) in growing patients. MATERIALS AND METHODS: Pediatric patients with TMJA treated by CCG from 2010.5 to 2021.7 were included in the study. CT scans were performed before and after operations with at least 1 year follow-up. The height of the mandibular ramus, menton deviation or retraction, osteotomy gap, etc. were measured by ProPlan CMF1.4 software. CCG growth, resorption, and relapse were evaluated and analyzed with influencing factors such as age, ostectomy gap, etc. by generalized estimating equation. RESULTS: There were 24 patients (29 joints) with an average age of 6.30 ± 3.13 years in the study. After operation, the mandibular ramus was elongated by 5.97 ± 3.53 mm. Mandibular deviation or retrusion was corrected by 4.82 ± 2.84 mm and 3.76 ± 2.97 mm respectively. After a mean follow-up of 38.91 ± 29.20 months, 58.62% CCG grew (4.18 ± 7.70 mm), 20.69% absorbed (2.23 ± 1.16 mm), and 20.69% re-ankylosed. The re-ankylosis was negatively correlated with the osteotomy gap (OR:0.348,0.172-0.702 95%CI, critical value = 6.10 mm). CCG resorption was positively correlated with the distance of CCG ramus elongation (OR:3.353,1.173-9.586 95%CI, critical value = 7.40 mm). CONCLUSIONS: An adequate osteotomy gap and CCG ramus elongation distance are the key factors for successful treatment of TMJA with jaw deformities in growing patients. CLINICAL RELEVANCE: TMJA affects mouth opening and jaw development in pediatric patients. The most common autogenous bone graft for pediatric patients is CCG due to its growth potential, convenient access and easy contouring. Also, it can simultaneously reconstruct the TMJ and improve jaw deformity by lengthening the mandibular ramus. But the growth of CCG is unpredictable. In this study, we explored several factors that may affect the absorption and re-ankylosis of CCG, expecting to provide several suggestions to improve future CCG treatment.

Simultaneous standard total joint prosthesis reconstruction with SSRO and Le Fort I osteotomy in the treatment of unilateral temporomandibular joint ankylosis with jaw deformity: a case cohort study.

OBJECTIVE: Unilateral temporomandibular joint ankylosis with jaw deformity (UTMJAJD) may require simultaneous total joint prosthesis (TJP) reconstruction, sagittal split ramus (SSRO), and Le Fort I osteotomies. The purpose of this study was to evaluate outcomes in patients treated with these procedures. METHODS: Patients diagnosed UTMJAJD between 2016 and 2018 were selected for the study. Mandible-first procedure was performed after ankylosis release with TJP on the ankylosed side and SSRO on the contralateral side. Le Fort I osteotomy with and without genioplasty was lastly performed. Maximal incisor opening (MIO), facial symmetry, and jaw and condyle stability were compared before, after operation, and during follow-ups. RESULTS: Seven patients were included in the study. Their average chin deviation was 9.5 ± 4.2 mm, and maxillary cant was 5.1 ± 3.0°. After operation, jaw deformity significantly improved, with chin deviation corrected 7.6 ± 4.1 mm (p = 0.015) and advanced 5.9 ± 2.5 mm (p = 0.006). After an average follow-up of 26.6 ± 17.1 months, MIO significantly increased from 11.4 ± 9.3 to 35.7 ± 2.6 mm (p = 0.000). The occlusion was stable with no significant positional or rotational changes of the jaw (p > 0.05). There was no obvious condylar resorption during follow-ups. CONCLUSION: Simultaneous TJP reconstruction, SSRO, and Le Fort I osteotomy are reliable and effective methods for the treatment of UTMJAJD.

Organocatalytic Enantioselective Synthesis of Seven-Membered Ring with Inherent Chirality.

Inherent chirality is used to describe chiral cyclic molecules devoid of central, axial, planar, or helical chirality and has tremendous applications in chiral recognition and enantioselective synthesis. Catalytic and divergent syntheses of inherently chiral molecules have attracted increasing interest from chemists. Herein, we report the enantioselective synthesis of inherently chiral tribenzocycloheptene derivatives via chiral phosphoric acid (CPA)-catalyzed condensation of cyclic ketones and hydroxylamines. This chemistry paves the way to accessing the less stable derivatives of 7-membered rings with inherent chirality. A series of chiral tribenzocycloheptene oxime ethers was synthesized in good yields (up to 97 %) with excellent enantioselectivities (up to 99 % ee).

Enantioselective Nickel-Catalyzed Denitrogenative Transannulation En Route to N-N Atropisomers.

Nickel-catalyzed transannulation reactions triggered by the extrusion of small gaseous molecules have emerged as a powerful strategy for the efficient construction of heterocyclic compounds. However, their use in asymmetric synthesis remains challenging because of the difficulty in controlling stereo- and regioselectivity. Herein, we report the first nickel-catalyzed asymmetric synthesis of N-N atropisomers by the denitrogenative transannulation of benzotriazones with alkynes. A broad range of N-N atropisomers was obtained with excellent regio- and enantioselectivity under mild conditions. Moreover, density functional theory (DFT) calculations provided insights into the nickel-catalyzed reaction mechanism and enantioselectivity control.

Single cell landscape of parietal epithelial cells in healthy and diseased states.

The biology and diversity of glomerular parietal epithelial cells (PECs) are important for understanding podocyte regeneration and crescent formation. Although protein markers have revealed the morphological heterogeneity of PECs, the molecular characteristics of PEC subpopulations remain largely unknown. Here, we performed a comprehensive analysis of PECs using single-cell RNA sequencing (scRNA-seq) data. Our analysis identified five distinct PEC subpopulations: PEC-A1, PEC-A2, PEC-A3, PEC-A4 and PEC-B. Among these subpopulations, PEC- A1 and PEC-A2 were characterized as podocyte progenitors while PEC-A4 represented tubular progenitors. Further dynamic signaling network analysis indicated that activation of PEC-A4 and the proliferation of PEC-A3 played pivotal roles in crescent formation. Analyses suggested that upstream signals released by podocytes, immune cells, endothelial cells and mesangial cells serve as pathogenic signals and may be promising intervention targets in crescentic glomerulonephritis. Pharmacological blockade of two such pathogenic signaling targets, proteins Mif and Csf1r, reduced hyperplasia of the PECs and crescent formation in anti-glomerular basement membrane glomerulonephritis murine models. Thus, our study demonstrates that scRNA-seq-based analysis provided valuable insights into the pathology and therapeutic strategies for crescentic glomerulonephritis.

Palladium-Catalyzed Double N-Arylation to Access Unsymmetric N,N'-Bicarbazole Scaffolds.

Herein, the palladium-catalyzed double C-N coupling of 9H-carbazol-9-amines and 2,2'-dibromo-1,1'-biphenyl is reported. This protocol offers access to N,N'-bicarbazole scaffolds, which have frequently been used as linkers in the construction of functional covalent organic frameworks (COFs). A variety of substituted N,N'-bicarbazoles were synthesized in moderate to high yields based on this chemistry, and the potential application of this method was showcased by the synthesis of COF monomers like tetrabromide 4 and tetraalkynylate 5.

The hamburger-shape photocatalyst: thioxanthone-based chiral [2.2]paracyclophane for enantioselective visible-light photocatalysis of 3-methylquinoxalin-2(1H)-one and styrenes.

A new thioxanthone-based photocatalyst with a [2.2]paracyclophane skeleton and planar chirality has been developed. The catalyst has been successfully applied in the visible light-mediated enantioselective aza Paternò-Büchi reactions of quinoxalinone and styrenes to produce azetidines. The structures of the catalyst derivatives were unequivocally determined by their single crystal X-ray crystallography analysis.

A prospective cohort study on decreased serum apelin-13 levels after human aneurysmal subarachnoid hemorrhage: associations with severity and prognosis.

Apelin-13 may have neuroprotective effects. We aimed to determine whether serum apelin-13 could serve as a potential biomarker for severity, delayed cerebral ischemia (DCI), and prognosis after human aneurysmal subarachnoid hemorrhage (aSAH). In this prospective, observational, cohort, single-center study of 139 patients with aSAH and 139 healthy individuals, serum apelin-13 levels were determined. The indicators of stroke severity were the Hunt-Hess scale and the modified Fisher grading scale. The prognostic parameters were DCI and 6-month worse prognosis (Extended Glasgow Outcome Scale scores of 1-4). Using binary logistic regression analysis, the relationship between serum apelin-13 levels and prognosis was reported as odds ratios (ORs) with 95% confidence intervals (CIs). Under the receiver operating characteristic curve, prognostic abilities were shown as areas under the curve (AUCs) with 95% CIs. Serum apelin-13 levels were substantially lower in patients than in controls (median, 28.8 versus 48.6 ng/ml; P < 0.001), in patients with DCI than in non-DCI patients (median, 14.9 versus 31.6 ng/ml; P < 0.001), and in patients with worse prognosis than in those with good prognosis (median, 16.3 versus 33.7 ng/ml; P < 0.001). Serum apelin-13 levels were independently correlated with Hunt-Hess scores (beta, -6.836; 95% CI, -8.963-4.708; VIF, 2.219; P = 0.001) and modified Fisher scores (beta, -3.350; 95% CI, -6.151-0.549; VIF, 1.562; P = 0.019). Serum apelin-13 levels were an independent predictor of DCI (OR, 0.951; 95% CI, 0.914-0.990; P = 0.022) and worse prognosis (OR, 0.954; 95% CI, 0.916-0.993; P = 0.013). Serum apelin-13 levels significantly differentiated DCI and poor prognosis, with AUCs of 0.753 (95% CI, 0.656-0.850) and 0.791 (95% CI, 0.713-0.868) respectively. Using the Youden method, serum apelin-13 levels < 19.3 ng/ml distinguished the risk of DCI with 64.7% sensitivity and 77.1% specificity, and serum apelin-13 levels < 30.2 ng/ml discriminated the development of worse prognosis with 89.1% sensitivity and 63.4% specificity. Serum apelin-13 levels combined with Hunt-Hess scores and modified Fisher scores displayed a significantly higher AUC than any one of them for prognostic prediction (all P < 0.05). Decreased serum apelin-13 levels, which are strongly correlated with disease severity, independently predicted poor outcomes following aSAH, substantializing serum apelin-13 as a useful prognostic biomarker of aSAH.

Cynasibirolide A, One New Humulanolide Sesquiterpene from Cynanchum acutum subsp. sibiricum.

Cynasibirolide A (1), one new humulanolide sesquiterpene, together with four known analogs, asteriscanolide (2), (1S,8S)-8-hydroxyhumula-2Z,6E,9E-trien-1,12-olide (3), (1S,7R)-8-oxohumula-2Z,9E-dien-1,12-olide (4), and (+)-6,7,9,10-tetrahydroasteriscunolide (5) were isolated from the roots and rhizomes of Cynanchum acutum subsp. sibiricum. Their structures and configurations were elucidated by spectroscopic methods, including 2D-NMR techniques, and the structure of 1 was confirmed by single-crystal X-ray diffraction. All compounds were evaluated for their anti-complementary activity in vitro, and compound 3 exhibited anti-complement effect with CH50 value of 0.45 mM.

Development of a Deep Learning-Based Epiglottis Obstruction Ratio Calculation System.

Surgeons determine the treatment method for patients with epiglottis obstruction based on its severity, often by estimating the obstruction severity (using three obstruction degrees) from the examination of drug-induced sleep endoscopy images. However, the use of obstruction degrees is inadequate and fails to correspond to changes in respiratory airflow. Current artificial intelligence image technologies can effectively address this issue. To enhance the accuracy of epiglottis obstruction assessment and replace obstruction degrees with obstruction ratios, this study developed a computer vision system with a deep learning-based method for calculating epiglottis obstruction ratios. The system employs a convolutional neural network, the YOLOv4 model, for epiglottis cartilage localization, a color quantization method to transform pixels into regions, and a region puzzle algorithm to calculate the range of a patient's epiglottis airway. This information is then utilized to compute the obstruction ratio of the patient's epiglottis site. Additionally, this system integrates web-based and PC-based programming technologies to realize its functionalities. Through experimental validation, this system was found to autonomously calculate obstruction ratios with a precision of 0.1% (ranging from 0% to 100%). It presents epiglottis obstruction levels as continuous data, providing crucial diagnostic insight for surgeons to assess the severity of epiglottis obstruction in patients.

Bioactivity-Guided High Performance Counter-Current Chromatography and Following Semi-Preparative Liquid Chromatography Method for Rapid Isolation of Anti-Inflammatory Lignins from Dai Medicinal Plant, Zanthoxylum acanthopodium var. timbor.

The development of Dai medicine is relatively slow, and Zanthoxylum has great economic and medicinal value. It is still difficult to obtain medicinal components from the low-polarity parts of Zanthoxylum belonging to Dai medicine. In this study, we introduced one simple and quick strategy of separating target compounds from the barks of Z. acanthopodium var. timbor by high-performance countercurrent chromatography (HPCCC) with an off-line anti-inflammatory activity screening mode. The development of this strategy was based on the TLC-based generally useful estimation of solvent systems (GUESS) method and HPCCC in combination. This paper presented a rapid method for obtaining target anti-inflammatory compounds. Three lignins were enriched by HPCCC with an off-line inhibition mode of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 macrophage cells, using petroleum ether-ethyl acetate-methanol-water (3:2:3:2) as the solvent system. The results showed that this method was simple and practical and could be applied to trace the anti-inflammatory components of the low-polarity part in Dai medicine.

Temporomandibular joint disc repositioning and occlusal splint for adolescents with skeletal class II malocclusion: a single-center, randomized, open-label trial.

BACKGROUND: Temporomandibular joint (TMJ) disc repositioning through open suturing (OSu) is a new disc repositioning method. Its result for adolescents with condylar resorption and dentofacial deformities combined with and without postoperative occlusal splints (POS) has not been well studied. OBJECTIVE: This study was to evaluate and compare the effects of OSu with and without POS in the treatment of TMJ anterior disc displacement without reduction (ADDwoR) in adolescent skeletal Class II malocclusion. METHODS: A total of 60 adolescents with bilateral ADDwoR were enrolled in this study. They were randomly allocated into two groups: OSu with and without POS. Magnetic resonance imaging (MRI) and lateral cephalometric radiographs were used to measure changes in condylar height and the degree of skeletal Class II malocclusion from before operation and at 12 months postoperatively. Changes in these indicators were compared within and between the two groups. RESULTS: After OSu, both groups exhibited significant improvements in condylar height and occlusion at the end of 12 months follow-up (P < 0.05). The group of OSu with POS had significantly more new bone formation (2.83 ± 0.75 mm vs. 1.42 ± 0.81 mm, P < 0.001) and improvement in dentofacial deformity than the group of OSu only (P < 0.05). The new bone height was significantly correlated with POS (P < 0.001), the changes of SNB (P = 0.018), overjet (P = 0.012), and Wits appraisal (P < 0.001). CONCLUSION: These findings indicated that OSu can effectively stimulate condylar regeneration and improve skeletal Class II malocclusion in adolescents with bilateral ADDwoR. The results are better when combined with POS. TRIAL REGISTRATION: This trial was prospectively registered on the chictr.org.cn registry with ID: ChiCTR1900021821 on 11/03/2019.

[Evaluation of Extrathyroidal Extension of Papillary Thyroid Microcarcinoma With Three-Dimensional Tomographic Ultrasound Imaging].

Objective To evaluate extrathyroidal extension (ETE) in papillary thyroid microcarcinoma (PTMC) with three-dimensional tomographic ultrasound imaging (3D-TUI). Methods A total of 97 thyroid nodules of 79 patients with PTMC treated in PUMC Hospital from February 2016 to January 2018 were included in this study.Two ultrasound experts performed independent blinded assessment of the relationship between thyroid nodules and thyroid capsule by two-dimensional ultrasound (2D-US) and 3D-TUI.The results of 2D-US and 3D-TUI in evaluating ETE were compared with intraoperative findings and postoperative histological and pathological results. Results Among the 97 nodules,54 (55.7%) nodules had ETE.The diagnostic sensitivity (68.5% vs.37.0%;χ2=10.737,P=0.002),accuracy (74.5% vs.56.7%;χ2=6.686,P=0.015),and area under the receiver operating characteristic curve[0.761 (95%CI=0.677-0.845) vs.0.592 (95%CI=0.504-0.680);Z=3.500,P<0.001] of 3D-TUI were higher than those of 2D-US.However,3D-TUI and 2D-US showed no significant difference in the specificity (84.1% vs.81.4%;χ2=0.081,P=0.776),negative predictive value (67.9% vs.50.7%;χ2=3.645,P=0.066),or positive predictive value (84.1% vs.71.4%;χ2=1.663,P=0.240). Conclusion Compared with 2D-US,3D-TUI demonstrates increased diagnostic efficiency for ETE of PTMC.

The Asymmetric Buchwald-Hartwig Amination Reaction.

Over the past few decades, the Buchwald-Hartwig reaction has emerged as a powerful tool for forging C-N bonds, and has been vital to the pharmaceuticals, materials, and catalysis fields. However, asymmetric Buchwald-Hartwig amination reactions for constructing centered chirality, planar chirality, and axial chirality remain in their infancy owing to limited substrate scope and laggard ligand design. The recent surge in interest in the synthesis of C-N/N-N atropisomers, has witnessed a renaissance in asymmetric Buchwald-Hartwig amination chemistry as the first practical protocol for the preparation of C-N atropisomers. This review highlights reported asymmetric Buchwald-Hartwig amination protocols and provides a brief overview of their chemical practicality.

Atroposelective Synthesis of C-N Vinylindole Atropisomers by Palladium-Catalyzed Asymmetric Hydroarylation of 1-Alkynylindoles.

Transition-metal-catalyzed hydroarylation of unsymmetrical internal alkynes remains challenging because of the difficulty in controlling regioselectivity and stereoselectivity. Moreover, the enantioselective hydroarylation of alkynes using organoboron reagents has not been reported. Herein, we report for the first time that palladium compounds can catalyze the hydroarylation of 1-alkynylindoles with organoborons for the synthesis of chiral C-N atropisomers. A series of rarely reported vinylindole atropisomers was synthesized with excellent regio-, stereo- (Z-selectivity), and enantioselectivity under mild reaction conditions. The ready availability of organoborons and alkynes and the simplicity, high stereoselectivity, and good functional group tolerance of this catalytic system make it highly attractive.

Enantioselective Synthesis of N-N Atropisomers by Palladium-Catalyzed C-H Functionalization of Pyrroles.

The catalytic asymmetric construction of N-N atropisomeric biaryls remains a formidable challenge. Studies of them lag far behind studies of the more classical carbon-carbon biaryl atropisomers, hampering meaningful development. Herein, the first palladium-catalyzed enantioselective C-H activation of pyrroles for the synthesis of N-N atropisomers is presented. Structurally diverse indole-pyrrole atropisomers possessing a chiral N-N axis were produced with good yields and high enantioselectivities by alkenylation, alkynylation, allylation, or arylation reactions. Furthermore, the kinetic resolution of trisubstituted N-N heterobiaryls with more sterically demanding substituents was also achieved. Importantly, this versatile C-H functionalization strategy enables iterative functionalization of pyrroles with exquisite selectivity, expediting the formation of valuable, complex, N-N atropisomers.

An Ultrasound-based Prediction Model to Predict Ureterolysis during Laparoscopic Endometriosis Surgery.

STUDY OBJECTIVE: To develop a model, including clinical features and ultrasound findings, to predict the need for ureterolysis (i.e., dissection of the ureter) during laparoscopy for endometriosis. DESIGN: A retrospective observational study of patients who had undergone transvaginal ultrasound (TVS) according to the International Deep Endometriosis Analysis consensus and subsequent laparoscopy ± excision of endometriosis between January 2017 and February 2021 was conducted. SETTING: Sydney Medical School Nepean, University of Sydney, Nepean Hospital, and Blue Mountains Hospital, New South Wales, Australia. PATIENTS/PARTICIPANT: 177 patients. INTERVENTION: The demographic, clinical, TVS, and intraoperative data were extracted through electronic clinical records. MEASUREMENTS AND MAIN RESULTS: Multicategorical decision-tree and baseline models were built to choose the variables most correlated to the outcome under study. Receiver operating characteristic analysis was performed on the binary classification. Based on our results, we selected the variables performing with significant statistical differences (p <.05). During the study period, 177 consecutive patients were recruited and divided into 2 subgroups, ureterolysis (51.4%) and nonureterolysis (48.6%). Ureterolysis was noted in 87.5% of patients in which the left ovary was immobile (p <.001) and in 82.5% in which the right ovary was fixed (p <.001). For patients with right uterosacral ligament (USL) deep endometriosis (DE), ureterolysis was performed in 96.2% patients (p <.001) and 64.6% (p = .043) for left USL DE. Among patients with bowel DE, the proportion of patients undergoing ureterolysis was 95.5% (p <.001). The prognostic variables used in the final model to predict ureterolysis included dyschezia, absence of ovarian mobility, presence of right or left USL DE, and presence of bowel DE on TVS. According to the developed model, the baseline risk for performing ureterolysis is 20% in our sample. The overall model performance demonstrated an area under the receiver operating characteristic curve 0.82. CONCLUSION: Our study demonstrates that it is possible to predict the need for ureterolysis with clinical and sonographic data. Furthermore, patients presenting with a combination of the variables of our model (dyschezia, ovarian immobility, USL, and bowel DE lesions) have a high risk of ureterolysis. In contrast, patients without these features have a low risk (approximately 20%) of needing ureterolysis.