Terminal halogen-containing rod-like liquid crystals: Synthesis, self-assembly, photophysical and mechanochromism properties.

Five series of cyanostilbene-based rod-like liquid crystals containing one different terminal atom (H, F, Cl, Br and I) at one end and one terminal aliphatic chain with different numbers of carbon atoms at the other end were reported by Suzuki coupling and Knoevenagel reactions. The influence of terminal halogen atoms and terminal chain length on the self-assembly, AIE behavior, temperature-dependent emission and mechanochromism behavior was explored by POM, DSC, XRD, SEM, absorption spectra and emission spectra. All the compounds are enantiotropic liquid crystals. The lowest non-halogen substituted homologue exhibited solo N phase, but the higher non-halogen substituted homologues exhibited mesogenic transition from SmA phase to N phase upon rising temperature. All the lowest halogen substituted homologues exhibited mesogenic transition from SmA phase to N phase upon rising temperature and all the higher homologues only exhibited SmA. The distinct mesogenic phase transition could be attributed to the intermolecular interaction produced by terminal halogen and the rigidity of the terminal aliphatic chain. All the non-halogen substituted compounds and halogen substituted compounds with smaller terminal halogen atom (F, Cl and Br atom) exhibited AIE behaviors, whereas the iodinated compounds exhibited extremely weak emission in solution and aggregated states due to the heavy atoms effect. These compounds also exhibited distinct solid-state emission with blue or cyan fluorescence, which could be quenched by increasing temperature. The reversible mechanochromism behavior was also achieved in all the compounds. The mechanical force induced quench in emission in non-halogen substituted compounds and halogen substituted compounds with smaller terminal halogen atom (F, Cl and Br atom), whereas enhancement in iodinated compounds. The reversible mechanochromism behavior endowed these compounds with potential applications in rewritable paper and anti-counterfeiting. The interesting properties in these liquid crystals would be attributed to the balance of the halogen-halogen interactions, heavy atom effect, steric-hindrance effect and chain length. These investigations would be helpful to understand the relationship between chemical structures and properties.

Development and validation of a prediction model for all-cause mortality in maintenance dialysis patients: a multicenter retrospective cohort study.

BACKGROUND: The mortality risk varies considerably among individual dialysis patients. This study aimed to develop a user-friendly predictive model for predicting all-cause mortality among dialysis patients. METHODS: Retrospective data regarding dialysis patients were obtained from two hospitals. Patients in training cohort (N = 1421) were recruited from the Fifth Affiliated Hospital of Sun Yat-sen University, and patients in external validation cohort (N = 429) were recruited from the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine. The follow-up endpoint event was all-cause death. Variables were selected by LASSO-Cox regression, and the model was constructed by Cox regression, which was presented in the form of nomogram and web-based tool. The discrimination and accuracy of the prediction model were assessed using C-indexes and calibration curves, while the clinical value was assessed by decision curve analysis (DCA). RESULTS: The best predictors of 1-, 3-, and 5-year all-cause mortality contained nine independent factors, including age, body mass index (BMI), diabetes mellitus (DM), cardiovascular disease (CVD), cancer, urine volume, hemoglobin (HGB), albumin (ALB), and pleural effusion (PE). The 1-, 3-, and 5-year C-indexes in the training set (0.840, 0.866, and 0.846, respectively) and validation set (0.746, 0.783, and 0.741, respectively) were consistent with comparable performance. According to the calibration curve, the nomogram predicted survival accurately matched the actual survival rate. The DCA showed the nomogram got more clinical net benefit in both the training and validation sets. CONCLUSIONS: The effective and convenient nomogram may help clinicians quantify the risk of mortality in maintenance dialysis patients.

A study on matching supply and demand of ecosystem services in the Hexi region of China based on multi-source data.

To achieve the best management of the ecosystem and sustainable socioeconomic development, it is crucial to clarify the matching relationship between the supply and demand of ecosystem services (ESs). Four types of ESs were chosen for the Hexi region in this study: food supply, carbon sequestration, water yield, wind erosion control and sediment retention. We assessed the supply-demand and matching relationships of different ESs using the Integrated Valuation of Ecosystem Service and Tradeoffs (InVEST) model, the ESs supply-demand ratio and the four-quadrant model. Moreover, we also analyzed the supply-demand ratio of integrated ESs and their cold spots. The findings suggest that (1) from 2000 to 2020, the average supply of food supply, carbon sequestration, water yield, wind erosion control and sediment retention increased by 44.31 t/km2, 128.44 t/hm2, 14,545.94 m3/km2 and 0.14 kg/m2 respectively, which showed a spatial pattern of "high in the southeast and low in the northwest". The average demand for food supply and carbon sequestration increased by 1.33 t/km2 and 0.32 t/hm2 respectively, while the average demand for water yield and wind erosion control and sediment retention decreased by 2997.25 m3/km2 and 1.19 kg/km2 respectively. The spatial distribution is consistent with the layout of population density, production and residential areas, and fragile ecological areas. (2) The supply-demand ratio of food supply, carbon sequestration and water yield is greater than 0.095, which is in a state of oversupply, and the supply-demand ratio of wind erosion control and sediment retention is less than 0, which is in a state of shortage; all ESs are mainly in low-low spatial matching areas, mainly concentrated in the desert areas of the northwest in the Hexi region. (3) The supply-demand ratio of integrated ESs increased by 0.024, and the proportion of cold spots and sub-cold spots was more than 50% and concentrated in the northwest, while hot spots and sub-hot spots accounted for only about 16%, mainly distributed in the southern Qilian Mountains and some oasis areas.

LINC00467 mediates the 5-fluorouracil resistance in breast cancer cells.

Breast cancer is a prevalent global disease that requires the development of effective therapeutic approaches. The occurrence of 5-fluorouracil (5-FU) resistance in breast cancer is emerging, which urgently needs new way to overcome the obstacle. In this study, we validated that the expression of LINC00467 is up-regulated in the breast cancer patients and breast cancer cells. In addition, the high expression of LINC00467 is associated with the 5-FU resistance of breast cancer cells. Interestingly, LINC00467 induced the homologous recombination (HR) repair via promoting the expression of NBS1 in 5-FU resistant breast cancer cells. Furthermore, miR-205 was validated as a common target of LINC00467 and NBS1, indicating that LINC00467 may induce NBS1 via the miRNA-mRNA target. Importantly, we identified that XBP1, as a transcription factor, induced the expression of LINC00467, which resulted in the enhanced HR efficiency and 5-FU resistance. Silencing XBP1 sensitized the 5-FU resistant breast cancer cells to the 5-FU treatment, whereas the ectopic expression of LINC00467 abrogated the effect of XBP1 silencing. In conclusion, LINC00467 enhances the 5-FU resistance by inducing NBS1-mediated DNA repair. LINC00467 also mediates the function of XBP1 in 5-FU resistance in breast cancer cells.

ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy.

Diabetes nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide, and podocyte injury is the central contributor to the progression of DN. Despite the emerging evidence that has established the importance of podocyte endoplasmic reticulum (ER) stress in the pathogenesis of DN, abnormal protein O-GlcNAcylation is also augmented. Currently, the mechanism associating these two hyperglycemia-induced disorders remains poorly understood. This study intended to elucidate whether ER stress drives hyper-protein O-GlcNAcylation to cause podocyte injury in DN. We used both type 1 and type 2 DN models to confirm the occurrence of ER stress and excessive protein O-GlcNAcylation, and then podocyte purification was also conducted for further investigation. Nephroseq V5 data were mined and in vitro studies were applied to reveal the involvement of ER stress and hyper-O-GlcNAcylation in podocyte injury. Our results indicated that ER stress was induced in both type 1 and type 2 DN, and the human RNA-seq data from Nephroseq V5 showed that O-GlcNAcylation-related genes were significantly upregulated in the DN patients. We further demonstrated that ER stress occurred prior to hyper-O-GlcNAc modification and that pharmacologically inhibited protein O-GlcNAcylation can help decrease the podocyte apoptosis induced by hyperglycemia. Together, these discoveries will aid in uncovering the activation of the ER stress-O-GlcNAcylation axis in podocyte injury under DN, which will help open up new therapeutic approaches for preventing DN progression.

Different Results from Varied Angles: The Positive Impact of Work Connectivity Behavior After-Hours on Work Engagement.

With the development of communication technology and the COVID-19 pandemic, it has become increasingly common for employees to maintain work connectivity after-hours, which has a significant impact on their psychological state at work. However, most of the existing studies have not reached a consensus on the impact of work connectivity behavior after-hours on employees' psychological state at work, and the existing studies have led to theoretical and practical disagreements. Based on the Job Demands-Resources model, we built a two-path model of work autonomy and emotional exhaustion to explore the impact of work connectivity behavior after-hours on work engagement. In addition, we compared the differences between different workplace statuses (managers and ordinary employees). Through surveys and analyses of 257 employees, the results show that work connectivity behavior after-hours positively impacts employees' work engagement by increasing managers' work autonomy and reducing ordinary employees' emotional exhaustion. This study not only reveals that work connectivity behavior after-hours positively affects work engagement but also illustrates the differences in impact between managers and ordinary employees; these findings contribute to the development of a consensus on the influence of work connectivity behavior after-hours on employees' psychological state at work, which provides insights for organizations seeking to manage work connectivity behavior after-hours, for example, by adopting different connectivity management strategies for employees with different workplace statuses.

Prognostic Value of Nighttime Double Product in Nondialysis Chronic Kidney Disease With Hypertension.

BACKGROUND: Both nighttime systolic blood pressure and pulse rate are associated with adverse outcomes in patients with chronic kidney disease (CKD). However, nighttime double product (DP), which is the product of nighttime systolic blood pressure and pulse rate, has not yet been investigated in this context. The present study aimed to explore the prognostic value of nighttime DP for adverse outcomes in patients with CKD and hypertension. METHODS AND RESULTS: This retrospective cohort study included a total of 1434 patients with nondialysis CKD complicated by hypertension. The patients were enrolled in Zhuhai and Guangzhou, China, with a median follow-up of 23.8 months. Patient enrollment for the high or low nighttime DP group was performed on the basis of the cutoff value determined by time-dependent receiver operator characteristic curve analysis. The primary end point was a composite of major cardiovascular and cerebrovascular events, and the secondary end point was all-cause death and composite renal end point. The 24-hour circadian DP rhythm was established via multiple-component cosinor analysis. Cox regression was used to explore the association between nighttime DP and adverse outcomes. The DP of nondialysis patients with CKD and hypertension showed a diurnal rhythm, which varied with renal function. After adjustment, high nighttime DP was associated with a higher risk for major cardiovascular and cerebrovascular events (hazard ratio [HR], 5.823 [95% CI, 2.382-14.233]), all-cause death (HR, 4.978 [95% CI, 2.205-11.240]), and composite renal event (HR, 1.661 [95% CI, 1.128-2.447]), compared with low nighttime DP. These associations were independent of nighttime systolic blood pressure and PR. CONCLUSIONS: The present cohort study demonstrated that DP had diurnal fluctuations and nighttime DP was an important prognostic factor in nondialysis patients with CKD and hypertension, outperforming traditional risk factors, including systolic blood pressure and pulse rate.

Sarcopenia and cardiovascular diseases: A systematic review and meta-analysis.

Sarcopenia is an age-related disease and is often accompanied by other diseases. Now, many studies have shown that cardiovascular diseases (CVDs) may raise the incidence rate of sarcopenia. Therefore, the purpose of this study was to conduct a systematic review and meta-analysis to investigate the prevalence of sarcopenia in patients with CVDs compared with the general population, defined as relatively healthy non-hospitalized subjects. The databases of PubMed, Embase, Medline and Web of Science were searched for eligible studies published up to 12 November 2022. Two assessment tools were used to evaluate study quality and the risk of bias. Statistical analysis was conducted using STATA 14.0 and R Version 4.1.2. Thirty-eight out of the 89 629 articles retrieved were included in our review. The prevalence of sarcopenia ranged from 10.1% to 68.9% in patients with CVDs, and the pooled prevalence was 35% (95% confidence interval [95% CI]: 28-42%). The pooled prevalence of sarcopenia was 32% (95% CI: 23-41%) in patients with chronic heart failure (CHF), 61% (95% CI: 49-72%) in patients with acute decompensated heart failure (ADHF), 43% (95% CI: 2-85%) in patients with coronary artery disease, 30% (95% CI: 25-35%) in patients with cardiac arrhythmia (CA), 35% (95% CI: 10-59%) in patients with congenital heart disease and 12% (95% CI: 7-17%) in patients with unclassed CVDs. However, in the general population, the prevalence of sarcopenia varied from 2.9% to 28.6% and the pooled prevalence was 13% (95% CI: 9-17%), suggesting that the prevalence of sarcopenia in patients with CVDs was about twice compared with the general population. The prevalence of sarcopenia was significantly higher only in patients with ADHF, CHF and CA compared with the general population. There is a positive correlation between CVDs and sarcopenia. The prevalence of sarcopenia is higher in patients with CVDs than that in the general population. With global aging, sarcopenia has brought a heavy burden to individuals and society. Therefore, it is important to identify the populations with high-risk or probable sarcopenia in order to do an early intervention, such as exercise, to counteract or slow down the progress of sarcopenia.

Integrating transcriptomic and metabolomic analysis to understand muscle qualities of red swamp crayfish (Procambarus clarkii) under transport stress.

This study investigated the transport stress (crowding stress and duration) on the physicochemical properties, energy metabolism and antioxidant enzyme activities of the red swamp crayfish (Procambarus clarkii) tail muscle (CTM). Besides, transcriptomic and metabolomic were conducted to elucidate the possible mechanism of CTM alternations during transport stress. The survival rate of crayfish gradually decreased with the external crowding stress and crowding time increasing. The transport stress also led to the increased distance among muscle fibers, water mobility and energy consumption, and the decreased of water holding capacity (WHC), hardness of CTM. The hepatopancreas exhibited more sensitive to crowding stress than muscle. The multi-omics analysis revealed that transport stress could interfere the translation and protein folding functions of ribosomal proteins, fatty acid metabolism and degradation, physiological functions of mitochondria in CTM. This study could provide critical information to increase the understanding of the regulation mechanism of crayfish when subjected to transport stress.

Mitochondria-associated endoplasmic reticulum membranes promote mitochondrial fission through AKAP1-Drp1 pathway in podocytes under high glucose conditions.

Excessive mitochondrial fission in podocytes is a critical feature of diabetic nephropathy (DN). Mitochondria-associated endoplasmic reticulum membranes (MAMs) are contact sites between the endoplasmic reticulum (ER) and mitochondria, which are suggested to be related to mitochondrial function. However, the role of MAMs in mitochondrial dynamics disorder in podocytes remains unknown. Here, we firstly reported a novel mechanism of MAMs' effects on mitochondrial dynamics in podocytes under diabetic conditions. Increased MAMs were found in diabetic podocytes in vivo and in vitro, which were positively correlated with excessive mitochondrial fission. What's more, we also found that A-kinase anchoring protein 1 (AKAP1) was located in MAMs, and its translocation to MAMs was increased in podocytes cultured with high glucose (HG). In addition, AKAP1 knockdown significantly reduced mitochondrial fission and attenuated high glucose induced-podocyte injury through regulating phosphorylation of dynamin-related protein 1 (Drp1) and its subsequent mitochondrial translocation. On the contrary, AKAP1 overexpression in these podocytes showed the opposite effect. Finally, pharmacological inhibition of Drp1 alleviated excessive mitochondrial fission and podocyte damage in AKAP1 overexpressed podocytes. Our data suggest that MAMs were increased in podocytes under diabetic conditions, leading to excessive mitochondrial fission and podocyte damage through AKAP1-Drp1 signaling.

Increased thromboxane/prostaglandin receptors contribute to high glucose-induced podocyte injury and mitochondrial fission through ROCK1-Drp1 signaling.

Excessive mitochondrial fission in podocytes serves as a central hub for the pathogenesis of diabetic nephropathy (DN), and the thromboxane/prostaglandin receptor (TP receptor) plays a potential role in DN. However, regulation of the TP receptor during mitochondrial dynamics disorder in podocytes remains unknown. Here, we firstly reported novel mechanistic details of TP receptor effects on mitochondrial dynamics in podocytes under diabetic conditions. Expression of the TP receptor was significantly upregulated in podocytes under diabetic conditions both in vivo and in vitro. S18886 attenuated podocyte mitochondrial fission, glomerular injury and renal dysfunction in diabetic mice. Furthermore, inhibition of the TP receptor by both genetic and pharmacological methods dramatically reduced mitochondrial fission and attenuated podocyte injury induced by high glucose through regulating dynamin-related protein 1 (Drp1) phosphorylation and its subsequent translocation to mitochondria. In contrast, TP receptor overexpression and application of TP receptor agonist U46619 in these podocytes showed the opposite effect on mitochondrial fission and podocyte injury. Furthermore, treatment with Y27632, an inhibitor of Rho-associated kinase1 (ROCK1), significantly blunted more fragmented mitochondria and reduced podocyte injuries in podocytes with TP receptor overexpression or after U46619 treatment. Finally, pharmacological inhibition of Drp1 alleviated excessive mitochondrial fragmentation and podocyte damage in TP receptor overexpressing podocytes. Our data suggests that increased expression of the TP receptor can occur in a human cultured podocyte cell line and in podocytes derived from streptozotocin (STZ)-induced diabetic mice, which contributes to mitochondrial excessive fission and podocyte injury via ROCK1-Drp1 signaling.

Copper-catalyzed regioselective C2-H chlorination of indoles with para-toluenesulfonyl chloride.

A copper-catalyzed, pyrimidine directed regioselective C-H chlorination of indoles with para-toluenesulfonyl chloride (TsCl) has been developed. The reactions proceeded smoothly in the presence of 20 mol% of Cu(OAc)2 as the catalyst and TsCl as the chlorine source, delivering C2-chlorinated indoles with structural diversity in moderate to excellent yields. Mechanistic studies suggested that single electron transfer (SET) from Cu(II) to TsCl accompanied by the release of the p-toluenesulfonyl radical and the related Cu(III)Cl species might be involved in the reactions.

Effects of Enzymatic Konjac Glucomannan Hydrolysates on Textural Properties, Microstructure, and Water Distribution of Grass Carp Surimi Gels.

This present work investigated the influence of konjac glucomannan (KGM) enzymatic hydrolysates on the textural properties, microstructure, and water distribution of surimi gel from grass carp (Ctenopharyngodon idellus). The molecular weight (Mw) of KGM enzymatic hydrolyzed by ß-dextranase degraded from 149.03 kDa to 36.84 kDa with increasing enzymatic time. In the microstructure of surimi gels, KGM enzymatic hydrolysates with higher Mw showed entangled rigid-chains, while KGM enzymatic hydrolysates with lower Mw (36.84 kDa) exhibited swelled fragments. The hardness of surimi gel with a decline in KGM Mw exhibited first increasing then decreasing trends, while the whiteness of surimi gel increased. When KGM Mw decreased, the immobile water percentage of total signals decreased from 96.7% to 93.6%, and mobile water increased from 3.03% to 6.37%. In particular, the surimi gel with the addition of K2 showed better gel strength and water distributions. KGM enzymatic hydrolysates are expected to be used as a low-calorie healthy gel enhancer in surimi processing.

Review of bioinformatics in Azheimer's Disease Research.

Alzheimer's disease (AD) is a severe neurodegenerative disease with slow course of onset and deterioration with time. With the speedup of global aging, AD has become a disease that seriously threatens the physical health of the elderly; therefore, the effective prevention and treatments of AD is an extremely important area of study for researchers and clinicians. Rapid technological developments have promoted the analysis of various kinds of complex data sets using machine learning methods. The common machine learning algorithms, such as Lasso, SVM and Random Forest, are very important in AD research. To help accelerate AD-related research, we review some recent research progress on Alzheimer's disease, including database, image analysis, gene expression, etc., which can provide AD researchers with more comprehensive research methods.

Microwave-Assisted Ruthenium- and Rhodium-Catalyzed Couplings of α-Amino Acid Ester-Derived Phosphinamides with Alkynes.

Two different types of new phosphinamide α-amino ester derivatives have been prepared in moderate to high yields via ruthenium(II) and rhodium(III)-catalyzed ortho-C-H functionalization under microwave irradiation. Specifically, the ortho-alkenylated phosphinamides were produced through coupling of phosphinamides containing an α-substituted or α,α-disubstituted α-amino ester with internal alkynes under ruthenium catalysis. In contrast, Ru and the more effective Rh-catalyzed coupling of the α-unsubstituted glycine ester phosphinamide with alkynes resulted in formation of oxidative annulation products, phosphaisoquinolin-1-ones. The developed methods feature the use of easily accessible starting materials, short reaction time, exclusive E-stereoselectivity (for ortho-alkenylation) and good functional group tolerance. The alkenylation reaction was readily scaled up to gram scale. Furthermore, the obtained alkenylated phosphinamide could be transformed into P-containing dipeptides through hydrolysis of the ester group in the catalysis product and subsequent condensation with an α-amino ester.

A Novel Homozygous Frameshift Mutation in ITGB3 Causes Glanzmann's Thrombasthenia.

The objective of this study was to elucidate the molecular characteristics of a Chinese family with Glanzmann's thrombasthenia (GT). The proband was diagnosed with GT based on clinical manifestations, platelet aggregation, and the expression of CD41 and CD61 in platelets. Whole-exome and Sanger sequencing were used to detect genetic defects related to GT in the proband and the family of the pedigree. Whole-exome sequencing showed a c.1784-1802delinsGTCACA, p. S595Cfs*70 homozygous mutation in exon 11 of the ITGB3 gene in the proband. Heterozygous mutations were found in the proband's parents, grandmother, uncle, aunt, and younger brother. This novel p. S595Cfs*70 ITGB3 gene mutation is not present in the 1000 Genomes and ExAC databases.

Quantitative proteomics insights into gel properties changes of myofibrillar protein from Procambarus clarkii under cold stress.

The impacts of cold stress (4 â„ƒ for 0 h, 12 h, 24 h, 36 h and 48 h, respectively) on the components, structural and physical properties of myofibrillar protein (MP) gel from Procambarus clarkii were investigated. The physicochemical analysis indicated the secondary and tertiary structure of MP were unfolding to different degrees after cold stress when compared to the control. The MP gel hardness reached a maximum when the cold stress reached 24 h. Furthermore, the quantitative proteomics results indicated that 20 up-regulated differentially abundant proteins (DAPs) were detected in 24 h when compared to control, specifically include myosin light chain 1 (MLC1) and skeletal muscle actin 6. Additionally, the combined analysis confirmed that MLC1 and skeletal muscle actin 6 might play key roles in hardening shrimp meat under cold stress. The results could provide a theoretical reference for the changes in crayfish muscle quality during cold chain transportation.

Correction: Diastereoselective synthesis of chiral 3-substituted isoindolinones via rhodium(III)-catalyzed oxidative C-H olefination/annulation.

Correction for 'Diastereoselective synthesis of chiral 3-substituted isoindolinones via rhodium(iii)-catalyzed oxidative C-H olefination/annulation' by Xue-Hong Li et al., Org. Biomol. Chem., 2021, DOI: 10.1039/d1ob00656h.