Hydroxymethylation hydroxylation of 1,3-diarylpropene through a catalytic diastereoselective Prins reaction: cyclization logic and access to brazilin core.

A catalytic diastereoselective Prins reaction for hydroxymethylation and hydroxylation of 1,3-diarylpropene was successfully utilized to prepare various 1,3-dioxanes 7 in 14-88% yields. Take advantage of the synthetic intermediate 7h, the key B/C rings in brazilin core could be constructed by the sequential of Friedel-Crafts/Ullmann-Ma rather than Ullmann-Ma/Friedel-Crafts reactions.

Divergent Total Syntheses of Lycorine Alkaloids via a Sequential C-H Functionalization Strategy.

A Pd-catalyzed one-pot sequential C-H functionalization strategy was utilized to prepare four lycorine alkaloids and one pseudo-lycorine alkaloid from the common intermediate 4. By switching the followed oxidative conditions of air, DMSO/H2O/I2, and DMSO/O2, based on the Pd(PPh3)4/K2CO3/toluene catalytic system, three key intermediates 12a, 12b, and 12c with different substitution patterns could be obtained in a well-controlled manner. As a result, four natural products γ-lycorane, hippadine, anhydrolycorinone, and anhydrolycorine as well as a pseudo-lycorine alkaloid Δ(4a,10b)-6-oxodihydrolycorine were successfully synthesized within 10 steps through this divergent route.

Association of serum albumin with heart failure mortality with NYHA class IV in Chinese patients: Insights from PhysioNet database (version 1.3).

BACKGROUND: Studies have proved that low albumin level is associated with increased mortality in most diseases, such as chronic kidney disease and hepatic cirrhosis. However, the relationship between albumin and all-cause death in heart failure patients in China is still unclear. OBJECTIVES: We aimed to investigate the association between albumin level and 28-day mortality in Chinese hospitalized patients with NYHA IV heart failure. METHODS: A total of 2008 Chinese patients were included. The correlation between serum albumin level and mortality was tested using a cox proportional hazards regression model. The smooth curve fitting was used to identify non-linear relationships between serum albumin and mortality. The Forest plot analysis was used to assess the association between albumin and 28-day mortality in different groups. RESULTS: Compared with patients with NYHA II-III, patients with NYHA IV had lower albumin level and higher mortality within 28 days. The albumin on admission was independently and inversely associated with the endpoint risk, which remained significant (hazard ratio: 0.80; 95 % confidence interval: 0.66 to 0.96; p = 0.0196) after multivariable adjustment. The smooth curve fitting showed with the increase of albumin, the mortality within 28 days would decrease. A subgroup analysis found that the inverse association between the albumin level and risk of the mortality was consistent across the subgroup stratified by possible influence factors. CONCLUSION: Serum albumin level is negatively associated with 28-day mortality in hospitalized heart failure patients within NYHA IV in China, which can be used as an independent predictor.

LncRNA expression signature identified using genome-wide transcriptomic profiling to predict lymph node metastasis in patients with stage T1 and T2 gastric cancer.

BACKGROUND: Lymph node (LN) status is vital to evaluate the curative potential of relatively early gastric cancer (GC; T1-T2) treatment (endoscopic or surgery). Currently, there is a lack of robust and convenient methods to identify LN metastasis before therapeutic decision-making. METHODS: Genome-wide expression profiles of long noncoding RNA (lncRNA) in primary T1 gastric cancer data from The Cancer Genome Atlas (TCGA) was used to identify lncRNA expression signature capable of detecting LN metastasis of GC and establish a 10-lncRNA risk-prediction model based on deep learning. The performance of the lncRNA panel in diagnosing LN metastasis was evaluated both in silico and clinical validation methods. In silico validation was conducted using TCGA and Asian Cancer Research Group (ACRG) datasets. Clinical validation was performed on T1 and T2 patients, and the panel's efficacy was compared with that of traditional tumor markers and computed tomography (CT) scans. RESULTS: Profiling of genome-wide RNA expression identified a panel of lncRNA to predict LN metastasis in T1 stage gastric cancer (AUC = 0.961). A 10-lncRNA risk-prediction model was then constructed, which was validated successfully in T1 and T2 datasets (TCGA, AUC = 0.852; ACRG, AUC = 0.834). Thereafter, the clinical performance of the lncRNA panel was validated in clinical cohorts (T1, AUC = 0.812; T2, AUC = 0.805; T1 + T2, AUC = 0.764). Notably, the panel demonstrated significantly better performance compared with CT and traditional tumor markers. CONCLUSIONS: The novel 10-lncRNA could diagnose LN metastasis robustly in relatively early gastric cancer (T1-T2), with promising clinical potential.

Salicylaldehyde as an SET-HAT Bifunctional Photocatalyst for the Intermolecular Transalkylation of Phthalimide.

Salicylaldehyde works as an efficient photocatalyst for the intermolecular transalkylation of phthalimide. The well-designed dimethyl N-hydroxyphthalimide ester proves to be a good alkylation reagent. It inhibits the competing intramolecular alkylation of alkylating reagent, enabling the site-specific synthesis of N-substituted phthalimide.

Iron-Catalyzed Aerobic α,ß-Dehydrogenation.

An iron-catalyzed direct aerobic α,ß-dehydrogenation of carbonyls has been reported. The combination of tert-butyl nitrite and N-hydroxyphthalimide worked as the organo cocatalyst system; thus, no extra transition metal reagents are required. A large variety of lactams and flavanones as well as lactone and thiochromen-4-one could be produced via this method in high yields.

Endo/Exo-Controllable Photocyclization by EnT-SET-Switch.

CBZ6, a redox-neutral non-donor-acceptor-type organo-photocatalyst, presents a strong reductive potential with an oxidative potential of -2.16 V (vs SCE). It can work as a photosensitizer for both single-electron transfer and triplet energy transfer processes. This feature enables site-selective control in the intramolecular hydroarylation of acrylamides. Both 5-exo-trig and 6-endo-trig cyclization products could be prepared regiospecfically under mild conditions. No transition metal, halogen-containing reagents, or additional reductant or oxidant is involved. This process provides a concise and environmentally sustainable access to a series of oxindoles and dihydroquinolinones.

Depth-driven responses of microbial residual carbon to nitrogen addition approaches in a tropical forest: Canopy addition versus understory addition.

Canopies play an important role in nitrogen (N) redistribution in forest ecosystems, and ignoring the canopy's role might bias estimates of the ecological consequences of anthropogenic atmospheric N deposition. We investigated the effects of the approach of N addition (Canopy addition vs. Understory addition) and level of N addition (25 kg N ha-1yr-1 vs. 50 kg N ha-1yr-1) on microbial residual carbon (MRC) accumulation in topsoil and subsoil. We found that the response of MRC to both approach and level of N addition varied greatly with soil depth in a tropical forest over eight years of continuous N addition. Specifically, N addition enhanced the accumulation of fungal and total MRC and their contribution to soil organic C (SOC) pools in the topsoil, whereas it decreased the contribution of fungal and total MRC to SOC in the subsoil. The contrasting effects of N addition on MRC contribution at varying soil depths were associated with the distinct response of microbial residues production. Understory N addition showed overall greater effects on MRC accumulation than canopy N addition did. Our results suggest that the canopy plays an important role in buffering the impacts of anthropogenic atmospheric N deposition on soil C cycling in tropical forests. The depth-dependent response of microbial residues to N addition also highlights the urgent need for further studies of different response mechanisms at different soil depths.

Caffeine ameliorates the metabolic syndrome in diet-induced obese mice through regulating the gut microbiota and serum metabolism.

OBJECTIVE: Obesity is associated with gut microbiota disorders, which has been related to developing metabolic syndromes. The research aims to investigate the effects of caffeine treatment on insulin resistance, intestinal microbiota composition and serum metabolomic changes in high-fat diet (HFD)-induced obesity mice. METHODS: Eight-week-old male C57BL/6 J mice were fed a normal chow diet (NCD) or HFD with or without different concentrations of caffeine. After 12 weeks of treatment, body weight, insulin resistance, serum lipid profiles, gut microbiota and serum metabolomic profiles were assessed. RESULTS: Caffeine intervention improved the metabolic syndrome in HFD-fed mice, such as serum lipid disorders and insulin resistance. 16S rRNA Sequencing analysis revealed that caffeine increased the relative abundance of Dubosiella, Bifidobacterium and Desulfovibrio and decreased that of Bacteroides, Lactobacillus and Lactococcus to reverse HFD-fed obesity in mice. Additionally, Caffeine Supplementation also altered serum metabolomics, mainly focusing on lipid metabolism, bile acid metabolism and energy metabolism. Caffeine increased its metabolite 1,7-Dimethylxanthine, which was positively correlated with Dubosiella. CONCLUSIONS: Caffeine exerts a beneficial effect on insulin resistance in HFD-mice, and the underlying mechanism may be partly related to altered gut microbiota and bile acid metabolism.

Comparison of Three-Dimensional Navigation-Guided Percutaneous Iliosacral Screw and Minimally Invasive Percutaneous Plate for the Treatment of Zone II Unstable Sacral Fractures.

OBJECTIVE: The percutaneous IS screws and the minimally invasive percutaneous plate are the most popular internal methods for Zone II unstable sacral fractures. However, the choice of fixation remains controversial for orthopaedic surgeons. The purpose of study was to evaluate and compare the clinical results of percutaneous iliosacral (IS) screw fixation under three-dimensional (3D) navigation and minimally invasive percutaneous plate fixation in the treatment of Zone II unstable sacral fractures. METHODS: A retrospective study was performed, including 64 patients with Zone II unstable sacral fractures who underwent percutaneous IS screw fixation under 3D navigation (navigation group) and minimally invasive percutaneous plate fixation (plate group) from January 2011 and March 2021 in our department. The age, gender, fracture type, mechanism of injury, injury severity score (ISS), time from admission to operation, operative time, intraoperative blood loss, hospital stay, incision length, follow-up time, time to clinical healing, and complications were recorded and analyzed. Matta standard was used to assess fracture reduction outcomes. The Majeed function system assessed functional outcomes at the last follow-up. RESULTS: The average follow-up time was (14.42 ± 1.57) months in the navigation group and (14.79 ± 1.37) months in the plate group. No statistical difference between the two groups in age, gender, fracture type, mechanism of injury, ISS, time from admission to operation, and time to clinical healing. However, significant differences were detected in operative time, intraoperative blood loss, hospital stay, and incision length (p < 0.001). According to Matta standard at 2 days postoperatively, the excellent and good rate was 91.42% in the navigation group, and it was 93.10% in the plate group. There was no significant difference between the two groups (p = 0.961). According to Majeed function system at the follow-up, the excellent and good rate was 97.14% in the navigation group, and 93.10% in the plate group. The difference between the two groups was not statistically significant (p = 0.748). There were no neurovascular injuries associated with this procedure. The incidence of complications was 44.82% (13/29) in the plate group, while 14.28% (5/35) in the navigation group (p = 0.007). CONCLUSION: This study found that compared with minimally invasive percutaneous plate fixation, percutaneous IS screw fixation under 3D navigation is a suitable option for the treatment of Zone II unstable sacral fractures. This approach is characterized by its shorter operation time, less surgical trauma, less bleeding, less hospital time, and fewer complications.

The association between paraspinal muscle degeneration and osteoporotic vertebral compression fracture severity in postmenopausal women.

BACKGROUND: According to reports in the literature, osteoporotic vertebral compression fracture (OVCF) is associated with paraspinal muscle degeneration; however, the association between the severity of OVCF and paraspinal muscle degeneration is not clear. OBJECTIVE: The purpose of this study was to investigate the association between paraspinal muscle degeneration and OVCF severity in postmenopausal women. METHODS: Three hundred and seventy-six MRI images from 47 patients were collected and analyzed. Sagittal and axial coronal T2-weighted images were used to measure the fractured vertebra sagittal cross-sectional area (FSCSA), the adjacent normal vertebral body sagittal cross-sectional area (NSCSA), paraspinal muscle cross-sectional area (CSA), and the fat cross-sectional area (FCSA). The ratio of fractured vertebra compressed sagittal cross-sectional area (RCSA) and fatty infiltration ratio (FIR) was subsequently calculated. The formulas for RCSA and FIR calculations are as follows: RCSA = (NSCSA-FSCSA)/NSCSA; FIR = FCSA/CSA. RCSA and FIR represent the severity of OVCF and paraspinal muscle degeneration, respectively. RESULTS: The correlation between paraspinal muscle degeneration and OVCF severity was analyzed using the Pearson correlation, and multiple regression analysis was performed to explore related risk factors. OVCF severity was closely associated with paraspinal muscle degeneration (L3/4 FIR r= 0.704, P< 0.05; L4/5 FIR r= 0.578, P< 0.05; L5/S1 FIR r= 0.581, P< 0.05). Multiple regression analysis demonstrated that the risk factor for OVCF severity was L3/4 FIR (ß= 0.421, P= 0.033). CONCLUSION: OVCF severity was associated with the FIR of paraspinal muscles, and L3/4 FIR was a predictive factor for OVCF severity in postmenopausal women.

A Predictive Model for Chronic Hydrocephalus After Clipping Aneurysmal Subarachnoid Hemorrhage.

Chronic hydrocephalus after clipping aneurysmal subarachnoid hemorrhage (aSAH) often results in poor outcomes. This study was to establish and validate model to predict chronic hydrocephalus after aSAH by least absolute shrinkage and selection operator logistic regression. The model was constructed from a retrospectively analyzed. Two hundred forty-eight patients of aSAH were analyzed retrospectively in our hospital from January 2019 to December 2021, and the patients were divided into chronic hydrocephalus (CH) group (n=55) and non-CH group (n=193) according to whether occurred CH within 3 months. In summary, 16 candidate risk factors related to chronic hydrocephalus after aSAH were analyzed. Univariate analysis was performed to judging the risk factors for CH. The least absolute shrinkage and selection operator regression was used to filter risk factors. Subsequently, the nomogram was designed by the above variables. And area under the curve and calibration chart were used to detect the discrimination and goodness of fit of the nomogram, respectively. Finally, decision curve analysis was constructed to assess the practicability of the risk of chronic hydrocephalus by calculating the net benefits. Univariate analysis showed that age (60 y or older), aneurysm location, modified Fisher grade, Hunt-Hess grade, and the method for cerebrospinal fluid drainage, intracranial infections, and decompressive craniectomy were significantly related to CH ( P <0.05). Whereas 5 variables [age (60 y or older), posterior aneurysm, modified Fisher grade, Hunt-Hess grade, decompression craniectomy] from 16 candidate factors were filtered by LASSO logistic regression for further research. Area under the curve of this model was 0.892 (95% confidence interval: 0.799-0.981), indicating a good discrimination ability. Meanwhile, the result of calibration indicated a good fitting between the prediction probability and the actual probability. Finally, decision curve analysis showed a good clinical efficacy. In summary, this model could conveniently predict the occurrence of chronic hydrocephalus after aSAH. Meanwhile, it could help physicians to develop personalized treatment and close follow-up for these patients.

Correction: Efficiently increasing the radiative rate of TADF material with metal coordination.

Correction for 'Efficiently increasing the radiative rate of TADF material with metal coordination' by Xian-Bao Cai et al., Chem. Commun., 2022, 58, 8970-8973, https://doi.org/10.1039/D2CC02930H.

Fecal microbiota transplantation treatment for type 1 diabetes mellitus with malnutrition: a case report.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease. Not only genetics, but the intestinal environment affected by gut microbiota is also the key to pathogenesis. Besides the occurrence of diabetes, gut microbiota dysbiosis may also contribute to the development of diabetes-related complications. Fecal microbiota transplantation (FMT) is an emerging technique that had shown its potential as a treatment for metabolic disease. Here, we report the first case of T1DM with malnutrition and gastrointestinal symptoms treated with FMT. A 24-year-old T1DM patient suffered from poor blood glucose control, recurrent nausea and vomiting, severe malnutrition, and intractable constipation after insulin treatment. The clinical response of the patients after FMT was well, especially nausea and vomiting were significantly relieved. In addition, constipation, nutritional status, and blood glucose control (fasting blood glucose, HbA1c) gradually improved. A degree of similarity was found in gut microbiota composition between the patient and healthy donor after FMT while it was totally different before the treatment. Furthermore, pathway function analysis of MetaCYC database implies that the potential mechanism of the response of FMT may be driven by specific bacteria involved in several metabolic pathways that need further exploration. To sum up, we believe that the reconstruction of intestinal flora by FMT may be a new choice for the treatment of T1DM patients with malnutrition.

Efficiently increasing the radiative rate of TADF material with metal coordination.

Herein, a simple and straightforward method to reduce dramatically the lifetime of a pure organic thermally activated delayed fluorescence (TADF) material VIA metal coordination is demonstrated. We designed a mononuclear silver complex [Ag(PPh2CH3)(TCzBN-PyPz)]BF4 (1) with a new emissive TCzBN-PyPz ligand. Even though the ligand and the metal complex have very similar emissive efficiencies and maximal peaks, over three orders of magnitude shorter lifetime of 0.59 µs for the complex than 2074 µs for ligand were obtained. Compared to other methods, the present protocol seems to be simple and highly effective.

Adjuvant chemotherapy following combined induction chemotherapy and concurrent chemoradiotherapy improves survival in N2-3-positive nasopharyngeal carcinoma patients.

OBJECTIVE: This study aimed to explore the clinical value of adjuvant chemotherapy (ACT) following concurrent chemo-radiotherapy (CCRT) and induction chemotherapy (ICT) in loco-regionally advanced nasopharyngeal carcinoma (LANC). METHODS: We included 839 newly diagnosed LANC patients in this study. ICT plus CCRT (ICT + CCRT group) was administered to 443 patients, and 396 patients received ACT after ICT plus CCRT (ICT + CCRT + ACT group). Univariate and multivariate Cox regression analyses were carried out. Furthermore, propensity score matching (PSM) was applied to balance the study and control groups. RESULTS: A total of 373 pairs of LANC patients were obtained after PSM analysis. We found that ACT following ICT + CCRT has no significant effect on improving the survival of LANC patients. By further exploring the ICT + CCRT + ACT treatment protocol, we excluded N0-1-positive patients and re-performed PSM in the ICT + CCRT and ICT + CCRT + ACT groups. Each group consisted of 237 patients. Kaplan-Meier analysis revealed that there were differences between the ICT + CCRT and ICT + CCRT + ACT groups in terms of the 5-year overall survival (OS) (78.9% vs. 85.0%, P = 0.034), disease-free survival (DFS) (73.4% vs. 81.7%, P = 0.029), and distant metastasis-free survival (DMFS) (84.9% vs. 76.0%, P = 0.019). In addition, the ICT + CCRT + ACT group had a higher incidence of grade 3/4 acute leukocytopenia/neutropenia. CONCLUSION: Compared with ICT + CCRT, ACT following ICT plus CCRT can reduce distant metastasis of N2-3-positive LANC and improve the OS and DFS. The results demonstrated the feasibility and clinical utility of ACT following ICT plus CCRT.

Digoxin targets low density lipoprotein receptor-related protein 4 and protects against osteoarthritis.

OBJECTIVES: Dysregulated chondrocyte metabolism is closely associated with the pathogenesis of osteoarthritis (OA). Suppressing chondrocyte catabolism to restore cartilage homeostasis has been extensively explored, whereas far less effort has been invested toward enhancing chondrocyte anabolism. This study aimed to repurpose clinically approved drugs as potential stimulators of chondrocyte anabolism in treating OA. METHODS: Screening of a Food and Drug Administration-approved drug library; Assays for examining the chondroprotective effects of digoxin in vitro; Assays for defining the therapeutic effects of digoxin using a surgically-induced OA model; A propensity-score matched cohort study using The Health Improvement Network to examine the relationship between digoxin use and the risk of joint OA-associated replacement among patients with atrial fibrillation; identification and characterisation of the binding of digoxin to low-density lipoprotein receptor-related protein 4 (LRP4); various assays, including use of CRISPR-Cas9 genome editing to delete LRP4 in human chondrocytes, for examining the dependence on LRP4 of digoxin regulation of chondrocytes. RESULTS: Serial screenings led to the identification of ouabain and digoxin as stimulators of chondrocyte differentiation and anabolism. Ouabain and digoxin protected against OA and relieved OA-associated pain. The cohort study of 56 794 patients revealed that digoxin use was associated with reduced risk of OA-associated joint replacement. LRP4 was isolated as a novel target of digoxin, and deletion of LRP4 abolished digoxin's regulations of chondrocytes. CONCLUSIONS: These findings not only provide new insights into the understanding of digoxin's chondroprotective action and underlying mechanisms, but also present new evidence for repurposing digoxin for OA.

Vasohibin-2 promotes proliferation and metastasis of cervical cancer cells by regulating epithelial-mesenchymal transition / 南方医科大学学报

OBJECTIVE@#To explore the role of vasohibin-2 (VASH2) in regulation of proliferation and metastasis of cervical cancer cells.@*METHODS@#We analyzed the differentially expressed genes between cervical cancer cells with flotillin-1 overexpression and knockdown by RNA-seq combined with analysis of public databases. The expression levels of VASH2 were examined in normal cervical epithelial cells (HcerEpic), cervical cancer cell lines (HeLa, C-33A, Ca ski, SiHa and MS751) and fresh cervical cancer tissues with different lymph node metastasis status. We further tested the effects of lentivirus-mediated overexpression and interference of VASH2 on proliferation, migration, invasion and lymphatic vessel formation of the cervical cancer cells and detected the expression levels of key epithelial-mesenchymal transition (EMT) markers and TGF-β mRNA.@*RESULTS@#RNA-seq and analysis of public databases showed that VASH2 expression was significantly upregulated in cervical cancer cells exogenously overexpressing flotillin-1 (P < 0.05) and downregulated in cells with flotillin-1 knockdown (P < 0.05), and was significantly higher in cervical cancer tissues with lymph node metastasis than in those without lymph node metastasis (P < 0.01). In cervical cancer cell lines Ca Ski, SiHa, and MS751 and cervical cancer tissue specimens with lymph node metastasis, VASH2 expression was also significantly upregulated as compared with HcerEpic cells and cervical cancer tissues without lymph node metastasis (P < 0.05). Exogenous overexpression of VASH2 significantly promoted proliferation, migration, invasion and lymphatic vessel formation of cervical cancer cells, whereas these abilities were significantly inhibited in cells with VASH2 knockdown (P < 0.05). The cervical cancer cells overexpressing VASH2 showed significant down- regulation of e-cadherin and up- regulation of N-cadherin, Vimentin and VEGF-C, while the reverse changes were detected in cells with VASH2 knockdown (P < 0.05). TGF-β mRNA expression was significantly up-regulated in cervical cancer cells overexpressing VASH2 and down-regulated in cells with VASH2 knockdown (P < 0.001).@*CONCLUSION@#Flotillin-1 may participate in TGF-β signaling pathway-mediated EMT through its down-stream target gene VASH2 to promote the proliferation, migration, invasion and lymphatic vessel formation of cervical cancer cells in vitro.

Direct Synthesis of ß-Amino Aldehydes from Linear Allylic Esters Using O2 as the Sole Oxidant.

A tandem isomerization-anti-Markovnikov oxidation of linear allylic imidic esters is developed using bis(benzonitrile)palladium chloride as the catalyst and O2 as the sole oxidant, regiospecifically giving ß-amino aldehydes as the product. tert-Butyl nitrite works as a simple, and the only, redox cocatalyst. tBuOH proves to be a crucial solvent for achieving excellent yield and specificity toward anti-Markovnikov aldehyde products.

The Design of a Track Monitoring System for Sports Injury Rehabilitation Training.

To realize the remote monitoring design in the process of rehabilitation training for athletes after an injury using computer technology, using Visual Studio 2010 development platform, and using ASP as the development language, NET as the development framework, the injury rehabilitation of injured athletes for dynamic monitoring of information management system, and its functions, system architecture and other detailed design. This article identified six laboratory workers outside the sample as experimental subjects. The experimental subjects' blood oxygen flow, degree, and rate were measured in the normal condition, and the pulse wave was recorded. Then, the upper and lower limbs rehabilitation training robot developed by the laboratory was used for about 15 minutes of rehabilitation training with 3-gear difficulty. The results show that the data measured by the system are the same as the data measured by the Lu Yue brand finger clip type YX301 blood oxygen saturation detector and meet the design requirements. Conclusion. The monitoring accuracy of the system is high, the resistance signal waveform is basically consistent with the actual waveform, and the monitoring effect is good.