TFA-Promoted Cascade Sulfonylation/Rearrangement/Cyclization of 1,5-Diynols and Sodium Sulfinates to Construct Sulfonylated Benzo[b]fluorenes.

A novel conversion of 1,5-diynols into sulfonylated benzo[b]fluorenes is reported by a TFA-promoted cascade cyclization with sodium sulfinates under mild conditions. This strategy provides an efficient and practical approach for accessing various sulfonated benzo[b]fluorenes in moderate to excellent yields under metal-free conditions. On the basis of the control experimental results and density functional theory calculations, a possible cascade transformation mechanism consisting of the dehydration of propargylic alcohols, sulfonylation, allenylation, and Schmittel-type cyclization is proposed. It is worth noting that TFA played an important role in this cascade cyclization, which promoted C-SO2R bond cleavage in a propargylic sulfone intermediate to form allenyl sulfones, followed by Schmittel-type cyclization to give the target product.

Regional disparities, age-related changes and sex-related differences in knee osteoarthritis.

BACKGROUND: The objective of the study is to analyse the regions, age and sex differences in the incidence of knee osteoarthritis (KOA). METHODS: Data were extracted from the global burden of diseases (GBD) 2019 study, including incidence, years lived with disability (YLD), disability-adjusted life-years (DALYs) and risk factors. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in age standardized rate (ASR) of KOA. Paired t-test, paired Wilcoxon signed-rank test and spearman correlation were performed to analyze the association of sex disparity in KOA and socio-demographic index (SDI). RESULTS: There were significant regional differences in the incidence of knee osteoarthritis. In 2019, South Korea had the highest incidence of knee osteoarthritis (474.85,95%UI:413.34-539.64) and Thailand had the highest increase in incidence of knee osteoarthritis (EAPC = 0.56, 95%CI = 0.54-0.58). Notably, higher incidence, YLD and DALYs of knee osteoarthritis were associated with areas with a high socio-demographic index (r = 0.336, p < 0.001; r = 0.324, p < 0.001; r = 0.324, p < 0.001). In terms of age differences, the greatest increase in the incidence of knee osteoarthritis was between the 35-39 and 40-44 age groups. (EAPC = 0.52, 95%CI = 0.40-0.63; 0.47, 95%CI = 0.36-0.58). In addition, there were significant sex differences in the disease burden of knee osteoarthritis (P < 0.001). CONCLUSIONS: The incidence of knee osteoarthritis is significantly different with regions, age and sex.

Incidence, risk factors, and outcomes of recurrent focal segmental glomerulosclerosis in pediatric kidney transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Focal segmental glomerulosclerosis is the most prevalent acquired kidney disease leading to end-stage renal disease in children and has a propensity for recurring in the transplanted kidney. The recurrence of FSGS after kidney transplantation in children varies greatly. In addition, the risk factors and outcomes of recurrence of FSGS remain controversial. This study evaluated the recurrence rate, risk factors, and prognosis of FSGS after kidney transplantation in order to provide advice and assistance in clinical decision-making for pediatric kidney transplantation. METHODS: PubMed, Embase, Web of Science, CNKI, and other databases were searched from the establishment of the repository to March 2022. We extracted data on incidence, risk factors, and outcomes. RESULTS: The results showed that the recurrence rate of primary FSGS in children after renal transplantation was 48% (95% CI 36%-59%) and the recurrence rate of FSGS (all forms) was 35% (95% CI 17%-52%). The graft loss rate of primary FSGS in children after kidney transplantation was 29% (95% CI 17%-42%) and the graft loss rate of FSGS (all forms) was 29% (95% CI 4%-62%). 57% (95% CI 42%-73%) of pediatric patients with recurrent primary FSGS showed complete remission. Risk factor analyses showed that age of onset (SMD .69, 95% CI .20-1.19, p = .006) was related to the recurrence of primary FSGS, whereas the living related donor was not a risk factor for recurrent primary FSGS in pediatrics after kidney transplantation (OR 1.22, 95% CI .48-3.10, p = .674). CONCLUSIONS: The recurrence rate and graft loss rate of FSGS in children after kidney transplantation were relatively high. Age at onset was associated with a risk for recurrent primary FSGS, whereas the living related donor was not a risk factor for recurrent FSGS in pediatric kidney recipients.

Palladium-Catalyzed Intermolecular Dearomatization Annulation Cascade Reaction of Furans for Stereoselective Access to 2,5-Dihydrofurans.

A novel palladium-catalyzed intermolecular dearomatization of furans with alkynes via a three-component formal [3 + 2] spiroannulation/allylic substitution cascade reaction has been successfully developed for the stereoselective assembly of spiro 2,5-dihydrofuran frameworks. High step economy and efficacy as well as excellent stereoselectivity were achieved for a broad substrate scope. Two new C-C bonds and one new C-O bond were generated sequentially in a one-pot manipulation. The yielded spiro 2,5-dihydrofuran skeleton bearing a tetrasubstituted carbon center constitutes the core structure for plenty of useful natural products or corresponding analogues. This work represents a significant advancement in the dearomatization strategy for furan heterocycles and provides a practical methodology for expedited access to complex spiro dihydrofuran scaffolds.

Cascade Cyclization of 1,5-Diynols and (RO)2P(O)SH to Construct Benzo[b]fluorenyl S-Alkyl Phosphorothioates under Catalyst-Free Conditions.

An efficient and practical cascade cyclization of 1,5-diynols with (RO)2P(O)SH as the acid promoter and nucleophile under mild conditions was developed. A variety of highly substituted benzo[b]fluorenyl-containing S-alkyl phosphorothioates were successfully constructed in moderate to excellent yields. Furthermore, this protocol exhibited good functional group tolerance, a broad substrate scope, and potential practical applications, with water as the only byproduct. The reaction proceeded with allenyl thiophosphate as a key intermediate, followed by a Schmittel-type cyclization process to produce the target product.

Synthesis of gem-dibromo 1,3-oxazines by NBS-mediated electrophilic cyclization of propargylic amides.

We present a highly efficient and practical method for synthesizing gem-dibromo 1,3-oxazines through 6-endo-dig cyclization of propargylic amides, using N-bromosuccinimide (NBS) as an electrophilic source. The metal-free reaction can be conducted under mild conditions with good functional group compatibility, delivering excellent yields of the desired products. Mechanistic studies suggest that the reaction proceeds via a double electrophilic attack by NBS on the propargylic amide substrate.

Gender and socioeconomic disparities in global burden of chronic kidney disease due to glomerulonephritis: A global analysis.

AIM: To investigate the gender and socioeconomic disparities in the global burden of chronic kidney disease (CKD) due to glomerulonephritis from 1990 to 2019. METHODS: Data were extracted from the global burden of diseases (GBD) 2019 study, including incidence, prevalence and disability-adjusted life-years (DALYs). Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in age-standardized rate (ASR) of CKD due to glomerulonephritis. Paired t-test, paired Wilcoxon signed-rank test and Spearman correlation were performed to analyse the association and gender disparity in CKD due to glomerulonephritis. RESULTS: Globally, incident cases of CKD due to glomerulonephritis increased 81% from 9 557 397 in 1990 to 17 308 071 in 2019. The age-standardized incidence rate increased by 1.47 compared with 1990 and DALYs increased by 1.35 compared with 1990 (per 100 000). The number of patients with CKD due to glomerulonephritis in low-middle SDI (3829917) and middle SDI (6268817) regions accounts for more than 55% of the total cases. CKD due to glomerulonephritis caused a higher burden including the incidence rate (p < .0001) and DALY rate (p < .0001) in men compared to women. The age-standardized DALY rate was negatively correlated with SDI (ρ = -0.64, p < .001). In the analysis of risk factors for DALYs, male individuals had a larger burden of hypertension, high BMI and high sodium diet in the DALY rates than female subjects. CONCLUSION: The burden of CKD due to glomerulonephritis was more skewed towards developing and less developed economies and differed by gender, so certain nations should implement far more focused and targeted policies.

Incidence and risk factors for recurrent focal segmental glomerulosclerosis after kidney transplantation: a meta-analysis.

AIMS: To systematically review the incidence and risk factors for recurrent FSGS after kidney transplantation. METHODS: We searched PubMed, Embase, Medline, Web of Science, the Cochrane Library, CNKI, CBMdisc, Wanfang, and Weipu for case-control studies related to recurrent FSGS from the establishment until October 2022. The protocol was registered on PROSPERO (CRD42022315448). Data were analyzed using Stata 12.0, with odds ratios (counting data) and standardized mean difference (continuous data) being considered as effect sizes. If the I2 value was greater than 50%, the random-effects model was used; otherwise, a fixed-effects model was used. A meta-analysis on the incidence and risk factors for recurrent FSGS after kidney transplantation was performed. RESULTS: A total of 22 studies with 966 patients and 12 factors were included in the meta-analysis. There were 358 patients with recurrent FSGS and 608 patients without FSGS after kidney transplantation. The results showed that the recurrence rate of FSGS after kidney transplantation was 38% (95% CI: 31%-44%). Age at transplantation (SMD = -0.47, 95% CI -0.73 to -0.20, p = .001), age at onset (SMD = -0.31, 95% CI -0.54 to -0.08, p = .008), time from diagnosis to kidney failure (SMD = -0.24, 95% CI -0.43 to -0.04, p = .018), proteinuria before KT (SMD = 2.04, 95% CI 0.91 - 3.17, p < .001), related donor (OR 1.99, 95% CI 1.20 - 3.30, p = .007) and nephrectomy of native kidneys (OR 6.53, 95% CI 2.68 - 15.92, p < .001) were associated with recurrent FSGS, whereas HLA mismatches, duration of dialysis before KT, sex, living donor, tacrolimus use and previous transplantation were not associated with recurrent FSGS after kidney transplantation. CONCLUSIONS: The recurrence of FSGS after kidney transplantation remains high. Clinical decision-making should warrant further consideration of these factors, including age, original disease progression, proteinuria, related donor, and nephrectomy of native kidneys.

Three-Component Synthesis of Dioxaphosphorane-Fused Diphosphacycles Exhibiting Unique Dynamic Fluorescence "On/Off" Properties.

Rigidly planar polycyclic phosphacycles featuring an internal dioxaphosphorane are promising photofunctional materials. However, the lack of efficient synthetic methods resulted in limited structural diversities which significantly hampered extensive study. Herein, we report a straightforward three-component synthesis of novel dioxaphosphorane-fused diphosphacycles with distinctive photophysical properties. Control experiments and theory calculations were performed to account for a plausible reaction mechanism. We also systematically investigated the structure-property relationships of these unprecedented platforms by combining experiments (X-ray analysis, optical and redox properties) and theoretical computations. Based on their unique structure and properties, a novel fluorescent switch for pH sensing was revealed by a dynamic ring-opening/ring-closing process.

Total Synthesis of Mycalisine B.

The first total synthesis of the marine nucleoside Mycalisine B-a naturally occurring and structurally distinct 4,5-unsaturated 7-deazapurine nucleoside-has been accomplished in 10 linear steps with 27.5% overall yield from commercially available 1,2,3,5-tetra-O-acetyl-ribose and tetracyanoethylene. Key steps of the approach include: (1) I2 catalyzed acetonide formation from 1,2,3,5-tetra-O-acetylribose and acetone at large scale; (2) Vorbrüggen glycosylation using N4-benzoyl-5-cyano-6-bromo-7H-pyrrolo[2,3-d]pyrimidine as a nucleobase to avoid formation of N-3 isomer; (3) mild and scalable reaction conditions.

An Efficient Approach to Phosphorylated Isoindoline Fused with Triazoles via Zn-Catalyzed Cascade Cyclization of 2-Propynol Benzyl Azides and Diarylphosphine Oxides.

An efficient approach for the synthesis of phosphorylated isoindoline fused with triazoles via Zn(OTf)2-catalyzed cascade cyclization of easily prepared ortho-propynol benzyl azides and diarylphosphine oxides is developed. The transformation occurred smoothly in moderate to excellent yields and tolerated various propargylic alcohol substrates.

TMSBr-Promoted Cascade Cyclization of ortho-Propynol Phenyl Azides for the Synthesis of 4-Bromo Quinolines and Its Applications.

Difficult-to-access 4-bromo quinolines are constructed directly from easily prepared ortho-propynol phenyl azides using TMSBr as acid-promoter. The cascade transformation performs smoothly to generate desired products in moderate to excellent yields with good functional groups compatibility. Notably, TMSBr not only acted as an acid-promoter to initiate the reaction, and also as a nucleophile. In addition, 4-bromo quinolines as key intermediates could further undergo the coupling reactions or nucleophilic reactions to provide a variety of functionalized compounds with molecular diversity at C4 position of quinolines.

An Expeditious Total Synthesis of 5'-Deoxy-toyocamycin and 5'-Deoxysangivamycin.

In present paper, an expeditious total synthesis of naturally occurring 5'-deoxytoyocamycin and 5'-deoxysangivamycin was accomplished. Because of the introduction of a benzoyl group at N-6 of 4-amino-5-cyano-6-bromo-pyrrolo[2,3-d]pyrimidine, a Vorbrüggen glycosylation with 1,2,3-tri-O-acetyl-5-deoxy-ß-D-ribofuranose afforded a completely regioselective N-9 glycosylation product, which is unambiguously confirmed by X-ray diffraction analysis. All of the involved intermediates were well characterized by various spectra.

Abnormal expression of FLOT1 correlates with tumor progression and poor survival in patients with non-small cell lung cancer.

Recent studies have revealed that flotillin-1 (FLOT1) plays important roles in cancer progression. However, the role of FLOT1 in development and progression of non-small cell lung cancer (NSCLC) remains largely unknown. The objective of the current study was to investigate the expression pattern and clinicopathological significance of FLOT1 in patients with NSCLC. Real-time quantitative polymerase chain reaction was applied to examine FLOT1 mRNA expression in 52 pairs of NSCLC tissues and adjacent noncancerous tissues. Immunohistochemistry was performed to examine FLOT1 protein expression in paraffin-embedded tissues from 106 NSCLC patients. Statistical analyses were applied to evaluate the diagnostic value and associations of FLOT1 expression with clinicopathological characteristics. FLOT1 mRNA expression was evidently upregulated in NSCLC tissues compared with that in the adjacent noncancerous tissues. In the 106 cases of tested NSCLC samples, FLOT1 protein level was positively correlated with tumor size, tumor stage, and lymph node metastasis. Patients with higher FLOT1 expression had shorter overall survival time, whereas those with lower FLOT1 expression had longer survival time. Taken together, our findings indicate that FLOT1 may play an important role in NSCLC tumorigenesis. Further elucidation of the molecular mechanisms underlying the role of FLOT1 is warranted.

Risk factors for recurrent IgA nephropathy after renal transplantation: A meta-analysis.

Recurrent glomerulonephritis after renal transplantation is the third most common cause of allograft loss, the most frequent of which is associated with IgA nephropathy (IgAN). This study aims to provide a systematic review of the risk factors associated with recurrent IgAN after renal transplantation. We searched English and Chinese databases, including PubMed, Embase, Web of Science, CNKI, and others, and included all case-control studies involving risk factors for recurrent IgAN after renal transplantation from the databases' establishment to March 2022. Data were analyzed using the Stata 12.0. A total of 20 case-control studies were included in the meta-analysis, with 542 patients with recurrent IgAN and 1385 patients without recurrent IgAN. The results showed that donor age (standardized mean difference [SMD] -0.13 [95% CI -0.26, -0.001]; P = 0.048), patient age at transplantation (SMD -0.41 [95% CI -0.53, -0.29]; P < 0.001), time from diagnosis to end-stage renal disease (SMD -0.42 [95% CI -0.74, -0.10]; P = 0.010), previous transplantation (odds ratio [OR] 1.73 [95% CI 1.06, 2.81]; P = 0.027), living donor (OR 1.86 [95% CI 1.34, 2.58]; P < 0.001), related donor (OR 2.64, [95% CI 1.84, 3.79]; P < 0.001), tacrolimus use (OR 0.71 [95% CI 0.52, 0.98]; P = 0.035), basiliximab use (OR 0.39 [95% CI 0.27, 0.55]; P < 0.001), proteinuria (SMD 0.42 [95% CI 0.13, 0.71]; P = 0.005) and serum IgA level (SMD 0.48 [95% CI 0.27, 0.69]; P < 0.001) were associated with recurrent IgAN after renal transplantation. In general, tacrolimus and basiliximab use were protective factors against recurrent IgAN after renal transplantation, whereas donor age, patient age at transplantation, time from diagnosis to end-stage renal disease, previous transplantation, living donor, related donor, proteinuria, and serum IgA level were risk factors for recurrent IgAN after renal transplantation. Clinical decision making should warrant further consideration of these risk factors.

NBS-mediated bromination and dehydrogenation of tetrahydro-quinoline in one pot: scope and mechanistic study.

A facile and general approach was developed for the efficient construction of functionalized bromoquinolines by the dehydrogenation of tetrahydroquinolines using NBS as the electrophile and as oxidant. The cascade transformation proceeded with good functional group tolerance under metal-free conditions with a short reaction duration. Various tetrahydroquinolines bearing either electron-rich or electron-deficient groups at different positions were successfully converted into the corresponding target products in moderate to high yields under mild conditions. It is worth noting that the obtained polybromoquinolines could further undergo classic metal-catalyzed cross-coupling reactions with good regioselectivity. The Sonagashira coupling reaction occurred regioselectively in the C-6 position of the obtained products followed by a Suzuki coupling reaction to give multifunctionalized quinolines. The mechanism indicated that electrophilic bromination/radical dehydrogenation sequences occurred in one pot.

Electrochemical 1,3-Alkyloxylimidation of Arylcyclopropane Radical Cations: Four-Component Access to Imide Derivatives.

Herein, a general electrochemical radical-cation-mediated four-component ring-opening 1,3-alkyloxylimidation of arylcyclopropanes, acetonitrile, carboxylic acids, and alcohols is described, providing a facile and sustainable approach to quickly construct structurally diverse imide derivatives from easily available raw materials in an operationally simple undivided cell. This metal-catalyst- and oxidant-free single-electron oxidation strategy offers a green alternative for the formation of highly reactive cyclopropane-derived radical cations, and this protocol features a broad functional group tolerance.

Interference Expression of StMSD Inhibited the Deposition of Suberin and Lignin at Wounds of Potato Tubers by Reducing the Production of H2O2.

Superoxide dismutase (SOD) actively participates in the wound stress of plants. However, whether StMSD mediates the generation of H2O2 and the deposition of suberin polyphenolic and lignin at potato tuber wounds is elusive. In this study, we developed the StMSD interference expression of potato plants and tubers by Agrobacterium tumefaciens-mediated transformation. The StSOD expression showed a marked downregulation in StMSD-interference tubers, especially StCSD2 and StCSD3. The content of O2•- exhibited a noticeable increase together with the inhibition in H2O2 accumulation. Moreover, the gene expression levels of StPAL (phenylalanine ammonia-lyase) and StC4H (cinnamate-4-hydroxylase) were downregulated in StMSD-interference tubers, and less suberin polyphenolic and lignin depositions at the wounds were observed. Taken together, the interference expression of StMSD can result in less suberin polyphenolic and lignin deposition by inhibiting the disproportionation of O2•- to H2O2 and restraining phenylpropanoid metabolism in tubers.

Critical values of monitoring indexes for perioperative major adverse cardiac events in elderly patients with biliary diseases.

BACKGROUND: Major adverse cardiac events (MACE) in elderly patients with biliary diseases are the main cause of perioperative accidental death, but no widely recognized quantitative monitoring index of perioperative cardiac function so far. AIM: To investigate the critical values of monitoring indexes for perioperative MACE in elderly patients with biliary diseases. METHODS: The clinical data of 208 elderly patients with biliary diseases in our hospital from May 2016 to April 2021 were retrospectively analysed. According to whether MACE occurred during the perioperative period, they were divided into the MACE group and the non-MACE group. RESULTS: In the MACE compared with the non-MACE group, postoperative complications, mortality, hospital stay, high sensitivity troponin-I (Hs-TnI), creatine kinase isoenzyme (CK-MB), myoglobin (MYO), B-type natriuretic peptide (BNP), and D-dimer (D-D) levels were significantly increased (P < 0.05). Multivariate logistic regression showed that postoperative BNP and D-D were independent risk factors for perioperative MACE, and their cut-off values in the receiver operating characteristic (ROC) curve were 382.65 pg/mL and 0.965 mg/L, respectively. CONCLUSION: The postoperative BNP and D-D were independent risk factors for perioperative MACE, with the critical values of 382.65 pg/mL and 0.965 mg/L respectively. Consequently, timely monitoring and effective maintenance of perioperative cardiac function stability are of great clinical significance to further improve the perioperative safety of elderly patients with biliary diseases.

Simplified Analytical Model for Predicting Neutral Cross-Section Position of Lenticular Deployable Composite Boom in Tensile Deformation.

Foldable and deployable flexible composite thin-walled structures have the characteristics of light weight, excellent mechanical properties and large deformation ability, which means they have good application prospects in the aerospace field. In this paper, a simplified theoretical model for predicting the position of the neutral section of a lenticular deployable composite boom (DCB) in tensile deformation is proposed. The three-dimensional lenticular DCB is simplified as a two-dimensional spring system and a rigid rod, distributed in parallel along the length direction. The position of the neutral cross-section can be determined by solving the balance equations and geometric relations. In order to verify the validity of the theoretical model, a finite element model of the tensile deformation of a lenticular DCB was established. The theoretical prediction results were compared with the finite element calculation results, and the two results were in good agreement.