Stereoselective Fluoroalkylacylation of Alkynes via Cooperative N-Heterocyclic Carbene/Palladium Catalysis.

Herein, a cooperative N-heterocyclic carbene- and palladium-catalyzed three-component reaction of alkynes with aldehydes and fluoroalkyl iodides is developed. A series of biologically valuable CF2R-incorporated α-substituted enones was obtained in moderate to good yields. This mild catalytic method exhibits exclusive regio- and stereoselectivity, excellent functional group tolerance, and a broad substrate scope including terminal and internal alkynes. Mechanistic investigations disclose that this alkyne fluoroalkylacylation proceeds via a radical relay process in which vinyl iodides serve as putative reaction intermediates.

The association between circulating fatty acids and stroke in hypertensive patients.

BACKGROUND: Stroke is prevalent in hypertensive population. It has been suggested that unsaturated fatty acids (USFA) have protective effect on stroke. The effect of saturated fatty acids (SFAs) on stroke is still unclear. Therefore, we studied the relationship between circulating fatty acids and acute ischemic stroke (AIS) in hypertensive patients. METHODS: Eighty-nine pairs including 100 men and 78 women matched by sex and age were recruited. Each pair included a hypertensive patient within 48h of AIS onset and a hypertensive patient without stroke. Six circulating fatty acids were methylated before concentration determination which was repeated twice with percent recovery estimated. RESULTS: There were differences in educational level (P = 0.002) and occupation (P < 0.001) between stroke and non-stroke participants. All the 6 fatty acid levels were higher in non-stroke participants (P = 0.017 for palmitoleic acid, 0.001 for palmitic acid, <0.001 for linoleic acid, <0.001 for behenic acid, <0.001 for nervonic acid and 0.002 for lignoceric acid). In logistic regression analysis, AIS was inversely associated with fatty acid levels except for lignoceric acid. After adjustment for education and occupation, the palmitoleic acid and palmitic acid levels were no longer inversely associated with AIS. After further adjustment for systolic blood pressure, smoking, drinking, total cholesterol and triglyceride, the inverse associations of linoleic acid (OR = 0.965, 95%CI = 0.942-0.990, P = 0.005), behenic acid (OR = 0.778, 95%CI = 0.664-0.939, P = 0.009), nervonic acid (OR = 0.323, 95%CI = 0.121-0.860, P = 0.024) with AIS remained significant. CONCLUSIONS: Circulating fatty acids except lignoceric acid were inversely associated with AIS. Both USFAs and SFAs may have beneficial effect on stroke prevention in hypertensive population.

Palladium-catalysed fragmentary esterification-induced allylic alkylation of allyl carbonates and cyclic vinylogous anhydrides.

An unprecedented palladium-catalysed fragmentary esterification-induced allylic alkylation (FEAA) of cyclic vinylogous anhydrides (CVAs) and allyl carbonates has been disclosed. The protocol features broad sp3-rich scaffold tolerance, rendering highly functionalized 1,6 and 1,7-dicarbonyls in up to high yields and diastereoselectivities. Three-component FEAA is also well tolerant to generate 1,6-dicarbonyls through the addition of extra O/N-nucleophiles. Furthermore, cyclic allyl carbonate-involved FEAA provides an efficient approach for the synthesis of structurally complex medium-sized rings.

Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Erratum: Author correction to "Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy" Acta Pharm Sin B (2022) 4224-4234

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

[Neuropsychological development of large for gestational age infants at the age of 12 months]. / 大于胎龄儿12æœˆé¾„ç¥žç»å¿ƒç†å‘è‚²çŠ¶å†µç ”ç©¶.

OBJECTIVES: To investigate the level of neuropsychological development in large for gestational age (LGA) infants at the age of 12 months. METHODS: The infants, aged 12 to <13 months, who attended the Outpatient Service of Child Care in the First Affiliated Hospital of Shandong First Medical University from December 2021 to June 2023, were enrolled as subjects. According to the gestational age and birth weight, they were divided into preterm appropriate for gestational age (AGA) group, preterm LGA group, early term AGA group, early term LGA group, full-term AGA group, and full-term LGA group. A modified Poisson regression analysis was used to investigate the association between LGA and neuropsychological development outcome at 12 months of age. RESULTS: After adjustment for confounding factors, compared with the full-term AGA group at the age of 12 months, the full-term LGA group had a significant increase in the risk of language deficit (RR=1.364, 95%CI: 1.063-1.750), the early term LGA group had significant increases in the risk of abnormal gross motor, fine motor, language, and the preterm LGA group had significant increases in the risk of abnormal language, social behavior, and total developmental quotient (P<0.05); also, the early term AGA group had higher risks of developmental delay across all five attributes and in total developmental quotient at the age of 12 months (P<0.05); except for the language attribute, the preterm AGA group had higher risks of developmental delay in the other 4 attributes (P<0.05). CONCLUSIONS: The neuropsychological development of LGA infants with different gestational ages lags behind that of full-term AGA infants at 12 months of age, and follow-up and early intervention of such infants should be taken seriously in clinical practice.

Serum hyaluronic acid and procollagen III, N-terminal propeptide levels are highly associated with disease severity and predict the progression of COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. In order to early identify severe and critical patients, we retrospectively analyze the clinical characteristics and risk indicators of severe disease in patients with corona virus disease 2019 (COVID-19). Methods: A total of 420 confirmed COVID-19 patients were included in the study. According to the "Diagnosis and Treatment of novel coronavirus Pneumonia (10th Edition)", the cases were divided into mild group (n = 243) and severe group (n =177). Laboratory parameters were analyzed in combination with clinical data. Results: Male patients over 46 years who have smoking habits were more likely to suffer from severe COVID-19. Critically ill patients had lower lymphocyte counts and red blood cell counts, and higher white blood cell counts (P<0.05). Expectedly, serum inflammatory factors (NLR, PLR, LMR, CLR, PCT, CRP), coagulation markers (APTT, PT, TT, FIB, D-Dimer), Myocardial damage markers (hs-TNT, LDH) were significantly increased (P<0.05) in severe COVID-19 patients. Surprisedly, those patients showed obviously elevated levels of common tumor markers (ProGRP, CYFRA21-1, SCC, NSE) (P<0.05). In this case, the levels of tumor marker reflected more the condition of inflammation than the growth of tumor. More importantly, HA and PIIIN-P were highly associated with COVID-19 severity. The AUC of the ROC curve for the diagnosis of severe COVID-19 by HA and PIIIN-P was 0.826. Meanwhile, HA was positively correlated with myocardial damage markers (hs-TNT, LDH). PIIIN-P was positively correlated with myocardial damage markers (hs-TNT, LDH) and inflammatory factors (NLR, PLR, LMR, CLR, ProGRP, SCC, PCT, CRP). On the contrary, PIIIN-P was negatively correlated with pulmonary function indexes (oxygenation index and oxygen saturation of hemoglobin). Conclusion: HA and PIIIN-P are highly associated with disease severity and progression of COVID-19 and can be used as new markers for the prediction of severe COVID-19.

Ketones from aldehydes via alkyl C(sp3)-H functionalization under photoredox cooperative NHC/palladium catalysis.

Direct synthesis of ketones from aldehydes features high atom- and step-economy. Yet, the coupling of aldehydes with unactivated alkyl C(sp3)-H remains challenging. Herein, we develop the synthesis of ketones from aldehydes via alkyl C(sp3)-H functionalization under photoredox cooperative NHC/Pd catalysis. The two-component reaction of iodomethylsilyl alkyl ether with aldehydes gave a variety of ß-, γ- and δ-silyloxylketones via 1,n-HAT (n = 5, 6, 7) of silylmethyl radicals to generate secondary or tertiary alkyl radicals and following coupling with ketyl radicals from aldehydes under photoredox NHC catalysis. The three-component reaction with the addition of styrenes gave the corresponding ε-hydroxylketones via the generation of benzylic radicals by the addition of alkyl radicals to styrenes and following coupling with ketyl radicals. This work demonstrates the generation of ketyl radical and alkyl radical under the photoredox cooperative NHC/Pd catalysis, and provides two and three component reactions for the synthesis of ketones from aldehydes with alkyl C(sp3)-H functionalization. The synthetic potential of this protocol was also further illustrated by the late-stage functionalization of natural products.

Association between whole blood essential trace elements and cognitive function in older adults.

BACKGROUND: Essential trace elements (ETEs) are essential nutrients for keeping the nervous system functioning. Associations between ETEs and cognitive function are still inconclusive and limited. OBJECTIVES: We aimed to investigate the individual and joint associations between ETEs and cognitive function among older adults. METHODS: A population (N = 2181) at an average age≥ 65 from Yiwu cohort in China was available for this study. Whole blood chromium (Cr), selenium (Se), manganese (Mn), and copper (Cu) concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), consisting of five specific cognitive domains: orientation, registry, attention and calculation, recall, and language and praxis. Linear regression, restricted cubic spline (RCS) analysis, and Bayesian kernel machine regression (BKMR) were used to analyze the individual and joint associations between ETEs and cognitive function. RESULTS: The association between Cr and MMSE score presented an inverted-U shape (Q3 versus Q1: ß = 0.774, 95 % CI: 0.297, 1.250; Q4 versus Q1: ß = 0.481, 95 % CI: 0.006, 0.956); and Cr was especially associated with the registry, recall, and language and praxis. Per IQR (36.32 µg/L) increase of Se was positively associated with the MMSE score (ß = 0.497, 95 % CI: 0.277, 0.717) and all five cognitive domains. The BKMR showed that the dose-response association between Se and cognitive function increased initially and then decreased with increasing Se concentration when fixed the other ETEs in median. ETEs mixture was positively associated with cognitive function, and Se (posterior inclusion probabilities, PIPs = 0.915) was the most important contributor within the ETEs mixture. CONCLUSIONS: The nonlinear association between Cr and cognitive function suggested further exploration of an appropriate concentration range for ETEs. A positive association between mixed ETEs and cognitive function is a reminder that their joint association should be considered. Further prospective studies or intervention studies are warranted to validate our findings in the future.

The specificity of body surface temperature of relevant back-shu points in patients with chronic persistent asthma based on infrared thermal imaging technology / 中国针灸

OBJECTIVE@#To detect the body surface temperature of the relevant back-shu points in patients with chronic persistent asthma by infrared thermal imaging technology, and observe the specific changes of the body surface temperature of the relevant back-shu points under the condition of lung disease.@*METHODS@#Forty-five patients with chronic persistent asthma (observation group) and 45 healthy subjects (control group) were selected. The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) were measured by BK-MT02A medical infrared thermography.@*RESULTS@#The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in the observation group was higher than that in the control group (P<0.01, P<0.05). The body surface temperature of bilateral Feishu (BL 13) and Geshu (BL 17) was higher than that of ipsilateral Pishu (BL 20) and Shenshu (BL 23) in the two groups (P<0.01, P<0.05). There was no statistically significant difference in body surface temperature between ipsilateral Feishu (BL 13) and Geshu (BL 17), between ipsilateral Pishu (BL 20) and Shenshu (BL 23) (P>0.05).@*CONCLUSION@#The pathological increase of body surface temperature of Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in patients with chronic persistent asthma indicates that above acupoints have specificity in reflecting lung diseases. The Feishu (BL 13) and Geshu (BL 17), which have significantly increased body surface temperature, not only provide objective basis for the pathological pathogenesis of "deficiency in origin and excess in symptom" in patients with chronic persistent asthma, but also reflect the different expressions of different acupoints on the same meridian for the lung diseases.

Prediction method for weaning outcomes based on machine learning and electrical impedance tomography / 医疗卫生装备

Objective To propose a method for predicting weaning outcomes based on machine learning and electrical impedance tomography(EIT).Methods Firstly,EIT image features were extracted from a total of 84 samples from 30 patients,and the important features screened with the extreme gradient boosting(XGBoost)algorithm were used as inputs to the model.Secondly,the prediction model was built with six machine learning methods,namely random forest(RF),support vector machines(SVM),XGBoost,gradient boosting decision tree(GBDT),logistic regression(LR)and decision tree(tree).Then the prediction model had its prediction performance evaluated by AUC,accuracy,sensitivity and specificity under imbalanced dataset,over-sampling balanced dataset and random under-sampling balanced dataset.Results In terms of AUC,accuracy and specificity,the model under the over-sampling balanced dataset and the random under-sampling balanced dataset behaved better than that under the imbalanced dataset(P＜0.05);in terms of sensitivity,the difference in model performance between the over-sampling balanced dataset and the imbalanced dataset was not statistically significant(P＞0.05),and the model performance under the random under-sampling balanced dataset decreased when compared with that under the imbalanced dataset(P＜0.05).There were no significant differences between the model performance under the over-sampling balanced dataset and that under the random under-sampling balanced dataset(P＞0.05).The model based on XGBoost behaved the best under the over-sampling balanced dataset,with an AUC of 0.769,an accuracy of 0.808,a sensitivity of 0.938 and a specificity of 0.600.Conclusion The method based on machine learning and EIT predicts weaning outcomes of patients with prolonged mechanical ventilation,and thus can be used for auxiliary decision support for clinicians to determine the appropriate timing of weaning.[Chinese Medical Equipment Journal,2023,44(10):1-6]

Comparison of ultrasound-guided lumbar plexus block and continuous adductor canal nerve block in total hip arthroplasty / 中国医师进修杂志

Objective:To compare the application value of ultrasound-guided lumbar plexus block (LPB) and continuous adductor canal nerve block (ACNB) in total hip arthroplasty (THA), and to explore the anesthesia scheme of THA.Methods:A prospective randomized controlled trial was used. Ninety patients who received THA admitted to in Lishui People′s Hospital from March 2019 to February 2022 were selected as the study subjects. According to the random number table method, 90 patients were divided into the test group and the control group, with 45 patients in each. The control group received LPB + general anesthesia, and the test group received ACNB + general anesthesia. By evaluating the hemodynamic parameters heart rate (HR) and mean arterial pressure (MAP) at the time of entry (T 1), osteotomy (T 2), prosthesis implantation (T 3) and immediately after surgery (T 4); the pain degree visual analogue score (VAS) at 6 h (S 1), 12 h (S 2), 24 h (S 3), 48 h (S 4) after awakening; the dosage of anesthetic drugs, the anesthetic effects of LPB and ACNB in THA were compared. Results:From T 2 to T 4, HR of patients in the two groups had a trend of increase: (85.24 ± 4.26) times/min vs. (86.13 ± 4.86) times/min, (83.82 ± 5.11) times/min vs. (85.16 ± 3.56) times/min and (81.64 ± 4.32) times/min vs. (82.24 ± 4.62) times/min, while MAP was in a downward trend: (86.54 ± 4.25) mmHg (1 mmHg = 0.133 kPa) vs. (85.35 ± 4.66) mmHg, (86.15 ± 3.92) mmHg vs. (84.86 ± 4.13) mmHg and (90.65 ± 5.25) mmHg vs. (92.12 ± 4.62) mmHg. The difference at different time points was statistically significant ( P<0.05). There was no statistically significant difference in HR, MAP and change trend between the two groups at different time ( P>0.05). The VAS score of the two groups increased from S 2 time point, and the difference between different time points was statistically significant ( P<0.05). The rising trend of VAS score in the test group was lower than that in the control group, and the VAS score at different time points was lower than that in the control group ( P<0.05). The dosage of sufentanil used in the test group was less than that in the control group: (114.37 ± 16.61) μg vs. (131.36 ± 18.31) μg, and the number of press of analgesia pump was less than that in the control group: 6.00 (5.00, 6.50) times vs. 8.00 (7.00, 9.00) times ( P<0.05). Conclusions:Ultrasound-guided LPB and ACNB could maintain hemodynamic stability in THA. Especially, ACNB could play an analgesic role within 48 h after THA and reduce the dosage of analgesic drugs.

A biomimetic liver cancer on-a-chip reveals a critical role of LIPOCALIN-2 in promoting hepatocellular carcinoma progression

Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.

Neuropsychological development of large for gestational age infants at the age of 12 months / 中国当代儿科杂志

OBJECTIVES@#To investigate the level of neuropsychological development in large for gestational age (LGA) infants at the age of 12 months.@*METHODS@#The infants, aged 12 to <13 months, who attended the Outpatient Service of Child Care in the First Affiliated Hospital of Shandong First Medical University from December 2021 to June 2023, were enrolled as subjects. According to the gestational age and birth weight, they were divided into preterm appropriate for gestational age (AGA) group, preterm LGA group, early term AGA group, early term LGA group, full-term AGA group, and full-term LGA group. A modified Poisson regression analysis was used to investigate the association between LGA and neuropsychological development outcome at 12 months of age.@*RESULTS@#After adjustment for confounding factors, compared with the full-term AGA group at the age of 12 months, the full-term LGA group had a significant increase in the risk of language deficit (RR=1.364, 95%CI: 1.063-1.750), the early term LGA group had significant increases in the risk of abnormal gross motor, fine motor, language, and the preterm LGA group had significant increases in the risk of abnormal language, social behavior, and total developmental quotient (P<0.05); also, the early term AGA group had higher risks of developmental delay across all five attributes and in total developmental quotient at the age of 12 months (P<0.05); except for the language attribute, the preterm AGA group had higher risks of developmental delay in the other 4 attributes (P<0.05).@*CONCLUSIONS@#The neuropsychological development of LGA infants with different gestational ages lags behind that of full-term AGA infants at 12 months of age, and follow-up and early intervention of such infants should be taken seriously in clinical practice.

Intelligent nanotherapeutic strategies for the delivery of CRISPR system

CRISPR, as an emerging gene editing technology, has been widely used in multiple fields due to its convenient operation, less cost, high efficiency and precision. This robust and effective device has revolutionized the development of biomedical research at an unexpected speed in recent years. The development of intelligent and precise CRISPR delivery strategies in a controllable and safe manner is the prerequisite for translational clinical medicine in gene therapy field. In this review, the therapeutic application of CRISPR delivery and the translational potential of gene editing was firstly discussed. Critical obstacles for the delivery of CRISPR system in vivo and shortcomings of CRISPR system itself were also analyzed. Given that intelligent nanoparticles have demonstrated great potential on the delivery of CRISPR system, here we mainly focused on stimuli-responsive nanocarriers. We also summarized various strategies for CIRSPR-Cas9 system delivered by intelligent nanocarriers which would respond to different endogenous and exogenous signal stimulus. Moreover, new genome editors mediated by nanotherapeutic vectors for gene therapy were also discussed. Finally, we discussed future prospects of genome editing for existing nanocarriers in clinical settings.

Comparison of 25-gauge+ and 27-gauge+ micro-invasive vitrectomy for vitreoretinal diseases / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To comparatively analyze the efficacy and safety between 25-gauge(25G+)and 27G+ micro-invasive vitrectomy for the treatment of vitreoretinal diseases.METHODS: The clinical data of 89 cases(89 eyes)of vitreoretinal disease who received vitrectomy at our hospital from March 2019 to April 2022 were retrospectively analyzed. They were divided into two groups according to surgery. A total of 45 cases(45 eyes)who received 25G+ micro-invasive vitrectomy were included in group A, and 44 cases(44 eyes)who received 27G+ micro-invasive vitrectomy were included in group B. Vitrectomy time, operation time, preoperative and postoperative best corrected visual acuity(BCVA), intraocular pressure, subjective comfort evaluation results and complications of the both groups were analyzed.RESULTS: There were no differences in vitrectomy time of the two groups(P&#x003E;0.05), while the operation time of group B was shorter than that of group A(35.50±14.27min vs. 41.73±14.25min, P=0.042). The postoperative BCVA of the two groups were better than that before operation(P&#x003C;0.05), while there was no significant difference between two groups(P&#x003E;0.05). The postoperative intraocular pressure of the two groups was lower than that before operation(P&#x003C;0.05), and it was slightly lower than group B at 1 and 7d after operation(P&#x003C;0.05). As for the subjective comfort evaluation results, the scores of group A was higher than that of group B at 1d after operation(6.13±1.20 vs. 3.45±1.17, P&#x003C;0.001); and there were no differences between two groups at 7d after operation(2.18±1.01 vs. 1.93±0.87, P=0.215). During the follow-up, 7(16%)eyes of incision leakage occurred in group A, of which 6(13%)eyes were transient hypotony, and 10(22%)eyes had conjunctival chemosis. In the group B, there was no incision leakage and transient hypotony, while conjunctival chemosis occurred in 2(4%)eyes at 1d after operation.CONCLUSION: Both 25G+ and 27G+ micro-invasive vitrectomy can improve visual acuity, stabilize intraocular pressure and be safe in patients with vitreoretinal disease. However, 27G+ micro-invasive vitrectomy has less leakage, stable intraocular pressure, shorter operation time and lower incidence of conjunctival chemosis.

Single cell sequencing revealed the mechanism of CRYAB in glioma and its diagnostic and prognostic value.

Background: We explored the characteristics of single-cell differentiation data in glioblastoma and established prognostic markers based on CRYAB to predict the prognosis of glioblastoma patients. Aberrant expression of CRYAB is associated with invasive behavior in various tumors, including glioblastoma. However, the specific role and mechanisms of CRYAB in glioblastoma are still unclear. Methods: We assessed RNA-seq and microarray data from TCGA and GEO databases, combined with scRNA-seq data on glioma patients from GEO. Utilizing the Seurat R package, we identified distinct survival-related gene clusters in the scRNA-seq data. Prognostic pivotal genes were discovered through single-factor Cox analysis, and a prognostic model was established using LASSO and stepwise regression algorithms. Moreover, we investigated the predictive potential of these genes in the immune microenvironment and their applicability in immunotherapy. Finally, in vitro experiments confirmed the functional significance of the high-risk gene CRYAB. Results: By analyzing the ScRNA-seq data, we identified 28 cell clusters representing seven cell types. After dimensionality reduction and clustering analysis, we obtained four subpopulations within the oligodendrocyte lineage based on their differentiation trajectory. Using CRYAB as a marker gene for the terminal-stage subpopulation, we found that its expression was associated with poor prognosis. In vitro experiments demonstrated that knocking out CRYAB in U87 and LN229 cells reduced cell viability, proliferation, and invasiveness. Conclusion: The risk model based on CRYAB holds promise in accurately predicting glioblastoma. A comprehensive study of the specific mechanisms of CRYAB in glioblastoma would contribute to understanding its response to immunotherapy. Targeting the CRYAB gene may be beneficial for glioblastoma patients.

N-Heterocyclic Carbene Catalyzed Three-Component Reaction for the Synthesis of Multi-substituted Benzenes.

An N-heterocyclic carbene-catalyzed three-component reaction of ketone, acetylenedicarboxylate, and enal for the synthesis of multisubstituted benzenes has been developed. The key features of this reaction are mild reaction conditions and high efficiency and chemoselectivity. The corresponding pentasubstituted benzenes are obtained in good to high yields.

Inorganic Flame-Retardant Coatings Based on Magnesium Potassium Phosphate Hydrate.

A magnesium potassium phosphate hydrate-based flame-retardant coating (MKPC) is formulated by dead-burnt magnesium oxide (magnesia) and potassium dihydrogen phosphate (KH2PO4), behaving as a matrix. Constituents of the MKPC include wollastonite, vermiculite, aluminum fluoride, aluminum trihydroxide, and calcium carbonate. Some of the ingredients inter-react to produce mullite whiskers at high temperatures, despite an acid-base hydration induced reaction between magnesia and KH2PO4. The MKPC's thermal, corrosion-resistant, mechanical, and flame-resistant properties were analyzed using scanning electron microscopy, electrochemical corrosion testing, compression testing, thermogravimetric analysis, and freeze/thaw tests. The results show that with the molar ratio = 4 of magnesia to KH2PO4, MKPC demonstrates lower thermal conductivity (0.19 W/m K), along with better corrosion resistance, stronger compressive strength (10.5 MPa), and higher bonding strength (6.62 kgf/cm2) to the steel substrate. Furthermore, acceptable additives to the formulation could enhance its flame-retardancy and increase its mechanical strength as well. Mullite whisker formed from the interaction of wollastonite, aluminum trihydroxide, and aluminum fluoride acts as an outer ceramic shield that enhances mechanical strength and compactness. In addition, Mg-containing minerals with calcium carbonate treated at high temperatures, transform into magnesium calcium carbonate after releasing CO2. At the optimum composition of MKPC (magnesia/KH2PO4 molar ratio = 4; wollastonite:vermiculite = 20:10 wt.%; aluminum trihydroxide = 10 wt.%; and calcium carbonate = 5 wt.%), coated on a steel substrate, the flame-resistance limit results exhibit below 200 °C on the back surface of the steel substrate after one hour of flaming (ca. 1000 °C) on the other surface, and the flame-resistance rating results demonstrate only 420 °C on the back surface of the steel substrate after three hours of flaming (>1000 °C) on the other surface. Both requirements for the flame-resistance limit and three-hour flame-resistance rating are met with the optimum compositions, indicating that MKPC plays an effective role in establishing flame-retardancy.

Pathogenesis and Drug Intervention of Diabetic Cardiomyopathy： A Review / 中国实验方剂学杂志

Diabetic cardiomyopathy， one of the cardiovascular complications of diabetes， is characterized by cardiac systolic and diastolic dysfunction at the early stage， which can later develop into heart failure. Due to the high incidence and mortality， it has been a hot topic in recent years. The pathogenesis of diabetic cardiomyopathy is complicated. It has been proved related to abnormal glucose and lipid metabolism， cardiac insulin resistance， mitochondrial dysfunction， abnormal calcium homeostasis， activation of renin-angiotensin-aldosterone system， increased oxidative stress， endoplasmic reticulum stress， inflammation， autophagy， and so on. The specific pathogenesis remains unclear. Currently， the diabetic cardiomyopathy is mainly tackled with both western medicine and traditional Chinese medicine （TCM）. Traditional western medicine has no specific remedy for diabetic cardiomyopathy， and the resulting side effect cannot be neglected. In order to improve the efficacy and reduce the side effects， researchers have tried some potential medical treatments， such as vaspin， melatonin， Coenzyme Q10， and non-coding RNA， which still need further clinical trials. Diabetic cardiomyopathy is not recorded in ancient TCM books. According to the symptoms and signs， modern physicians often consider it as a "consumptive disease"， whose main therapeutic principles lie in benefiting Qi， tonifying Yin， activating blood， and removing stasis. The individual Chinese herbs such as Astragali Radix and Salviae Miltiorrhizae Radix et Rhizoma and Chinese herbal compounds like Huotan Jiedu Tongluoyin are effective in protecting the heart. But there are few studies exploring the pharmacodynamic mechanisms of TCM. With the continuous emergence of new drugs， the integration of TCM with western medicine may be a more promising treatment in the future. In conclusion， the pathogenesis of diabetic cardiomyopathy is unclear， and there is a lack of effective prevention and treatment. This paper reviewed the latest findings in pathogenesis and treatment of diabetic cardiomyopathy， in order to provide reference for further research.