Rapid and effective hemostatic materials have received wide attention not only in the battlefield but also in hospitals and clinics. Traditional hemostasis relies on materials with little ...designability which has many limitations. Nanohemostasis has been proposed since the use of peptides in hemostasis. Nanomaterials exhibit excellent adhesion, versatility, and designability compared to traditional materials, laying a good foundation for future hemostatic materials. This review first summarizes current hemostatic methods and materials, and then introduces several cutting‐edge designs and applications of nanohemostatic materials such as polypeptide assembly, electrospinning of cyanoacrylate, and nanochitosan. Particularly, their advantages and working mechanisms are introduced. Finally, the challenges and prospects of nanohemostasis are discussed.
Some emerging nanohemostatic techniques are summarized. Nanotechnology can increase the degree of interface bonding and enhance adhesion, reduce the amount of medication used to reduce toxic effects, and interact with blood cells or blood components to design a more effective means of hemostasis. The development of nanohemostatic technology can have great potential in the future.
Vibralactone is isolated from the basidiomycete fungus Boreostereum vibrans as one of the strongest lipase inhibitors. Its unusual β‐lactone‐fused bicycle is derived from an aryl ring moiety by an ...oxidative ring‐expansion prior to an intramolecular cyclization. Herein, we report the discovery of the cyclase VibC which belongs to the α/β‐hydrolase superfamily and is involved in the vibralactone biosynthesis. Biochemical and crystal studies suggest that VibC may catalyze an aldol or an electrocyclic reaction initiated by the Ser‐His‐Asp catalytic triad. For the aldol and pericyclic chemistry in living cells, VibC is a unique hydrolase performing the carbocycle formation of an oxepinone to a fused bicyclic β‐lactone. This presents a naturally occurring, new enzymatic reaction in both aldol and hydrolase (bio)chemistry that will guide future exploitation of these enzymes in synthetic biology for chemical‐diversity expansion of natural products.
The cyclization of an oxepinone (3) to form a fused bicyclic β‐lactone (1) proceeds by a ring‐opening aldol‐lactonization cascade or a pericyclic reaction driven by the Ser‐His‐Asp catalytic triad of the cyclase VibC from the basidiomycete Boreostereum vibrans.
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•A carbonate U-Pb age of 565.0 ± 5.5 Ma was obtained from the Dengying Formation.•New age is consistent with regional Ediacaran successions in the Yangtze Block.•New age aids in ...re-evaluating the chronostratigraphic framework of the Ediacaran successions.•New age leaves us hope of dating other Precambrian carbonates worldwide.
Precambrian sedimentary carbonate succession ages are challenging due to the lack of suitable fossil records and mineral chronometers and techniques. Here we present the first result for in situ LA-ICP-MS U–Pb dolomite dating from the Dengying Formation in the Mayuan area, Shaanxi Province, South China. The sample yields a date of 565.0 ± 5.5 Ma (2σ, MSWD = 2.8, n = 47). This age agrees well with regional Ediacaran successions in the Yangtze Block. The new ages are considered alongside regional correlations of Ediacaran successions in South China and help to re-evaluate the chronostratigraphic framework of the Dengying and Doushantuo Formation. It also opens a new window for dating those blind sedimentary carbonate strata, particularly during the Precambrian era.
Variable-rate coding schemes that support a variety of different rates while maintaining the same fundamental encoder/decoder architectures are of great interest in practical communication systems. ...Similar error-correcting code schemes are also in demand in quantum settings. However, generally, it is difficult to introduce the variable-rate coding schemes into the quantum coding domain attributed to two challenges: Obtaining new quantum codes from old ones systematically and sharing encoder-decoder components among the newly obtained quantum codes. In this correspondence, a multiple-rate coding scheme is introduced into the quantum coding domain, we achieve this goal by providing a systematic method to construct new non-homogeneous quantum LDPC codes of CSS type from an old one (named as the mother code) whose classical parity-check matrix (PCM) is row-circulant. The basic idea is to split rows of the highest-rate stabilizer elaborately to produce the stabilizer for lower rates, which ensures that the generated code family owns the same code length. More importantly, thanks to the nested stabilizer structures possessed by the resulting quantum codes, our method also enables a scalable stabilizer circuit to be shared among them.
Tricuspid regurgitation (TR) is a prevalent disease that triggers systemic pathological changes including cardiac, respiratory, hepatic and digestive, hematopoietic, renal and skin issues. The burden ...of extra-cardiac manifestations has not been well described in TR patients and the clinical impact is unknown.
Patients with severe or more-than-severe TR during hospitalization, who did not have any previous cardiac procedures, hemodynamically significant congenital heart disease or concomitant severe aortic or mitral valve disease, were retrospectively analyzed. Pre-specified criteria and diagnosis of baseline characteristics were used to evaluate the presence of extra-cardiac manifestations secondary to TR after excluding comorbidities that may also lead to corresponding abnormalities. Extra-cardiac involvements encompass respiratory, hepatic and, digestive, renal, hematopoietic and dermatic system. Staging criteria are defined as no extra-cardiac system involvement in Stage 1, one in Stage 2, at least two extra-cardiac involvements in Stage 3 and any end-stage organ failure in Stage 4. A telephone follow-up was conducted to record the composite endpoint namely all-cause death or cardiac rehospitalization after the index hospitalization.
A total of 258 patients were identified with a median age of 73 (interquartile range IQR: 62-83) years and 52.3% were female. Severe TR and more-than-severe TR patients accounted for 92.6% and 7.4% of the cohort. There were 20.5%, 27.5%, 37.6% and 14.3% of patients from Stage 1 to 4 respectively. The follow-up time was at a median of 251 (IQR: 183-324) days. TR Patients in Stage 3&4 were at an increased risk with borderline statistical significance to experience the composite endpoint compared to patients in Stage 1&2 (odds ratio OR 1.9, 95% confidence interval CI 1.0 to 3.7, P = 0.049).
Approximately half of patients with at least severe TR presented with two or more extra-cardiac systemic manifestations, which may incur a 1.9-fold higher risk of all-cause death or cardiac rehospitalization than TR patients with one or less extra-cardiac involvement.
In the early stages of nonalcoholic fatty liver disease (NAFLD), triglycerides accumulate in hepatocytes. Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step in hepatocyte triglyceride ...biosynthesis. DGAT2 antisense oligonucleotide (ASO) treatment improved hepatic steatosis dramatically in a previous study of obese mice. According to the 2‐hit hypothesis for progression of NAFLD, hepatic steatosis is a risk factor for nonalcoholic steatohepatitis (NASH) and fibrosis. To evaluate this hypothesis, we inhibited DGAT2 in a mouse model of NASH induced by a diet deficient in methionine and choline (MCD). Six‐week‐old genetically obese and diabetic male db/db mice were fed either the control or the MCD diet for 4 or 8 weeks. The MCD diet group was treated with either 25 mg/kg DGAT2 ASO or saline intraperitoneally twice weekly. Hepatic steatosis, injury, fibrosis, markers of lipid peroxidation/oxidant stress, and systemic insulin sensitivity were evaluated. Hepatic steatosis, necroinflammation, and fibrosis were increased in saline‐treated MCD diet–fed mice compared to controls. Treating MCD diet–fed mice with DGAT2 ASO for 4 and 8 weeks decreased hepatic steatosis, but increased hepatic free fatty acids, cytochrome P4502E1, markers of lipid peroxidation/oxidant stress, lobular necroinflammation, and fibrosis. Progression of liver damage occurred despite reduced hepatic expression of tumor necrosis factor alpha, increased serum adiponectin, and striking improvement in systemic insulin sensitivity. Conclusion: Results from this mouse model would suggest accumulation of triglycerides may be a protective mechanism to prevent progressive liver damage in NAFLD. (HEPATOLOGY 2007.)
CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic ...leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy. These were compared with 124 consecutive T-ALL/LBL patients who received allo-HSCT in CR following chemotherapy. The study revealed that both the CAR-T and chemotherapy cohorts exhibited comparable 2-year overall survival (OS) (61.9% 95% CI, 44.1-78.1 vs. 67.6% 95% CI, 57.5-76.9, p = 0.210), leukaemia-free survival (LFS) (62.3% 95% CI, 44.6-78.4 vs. 62.0% 95% CI, 51.8-71.7, p = 0.548), non-relapse mortality (NRM) rates (32.0% 95% CI, 19.0-54.0 vs. 25.3% 95% CI, 17.9-35.8, p = 0.288) and relapse incidence rates (8.8% 95% CI, 3.0-26.0 vs. 15.8% 95% CI, 9.8-25.2, p = 0.557). Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.
We describe a catalytic strategy for direct single C(sp3)–F bond alkylation of trifluoromethylbenzimidazoles under a photoinduced thiol catalysis process. The CO2 radical anion (CO2 •–) proved to be ...the most efficient single-electron reductant to realize such a transformation. The spin-center shift of the generated radical anion intermediate is the key step in realizing C–F bond activation under mild conditions with high efficiency.
(1) Lipases are catalysts widely applied in industrial fields. To sustain the harsh treatments in industries, optimizing lipase activities and thermal stability is necessary to reduce production ...loss. (2) The thermostability of
lipase (TLL) was evaluated via B-factor analysis and consensus-sequence substitutions. Five single-point variants (K24S, D27N, D27R, P29S, and A30P) with improved thermostability were constructed via site-directed mutagenesis. (3) The optimal reaction temperatures of all the five variants displayed 5 °C improvement compared with TLL. Four variants, except D27N, showed enhanced residual activities at 80 °C. The melting temperatures of three variants (D27R, P29S, and A30P) were significantly increased. The molecular dynamics simulations indicated that the 25-loop (residues 24-30) in the N-terminus of the five variants generated more hydrogen bonds with surrounding amino acids; hydrogen bond pair D254-I255 preserved in the C-terminus of the variants also contributes to the improved thermostability. Furthermore, the newly formed salt-bridge interaction (R27…E56) in D27R was identified as a crucial determinant for thermostability. (4) Our study discovered that substituting residues from the 25-loop will enhance the stability of the N-terminus and C-terminus simultaneously, restrict the most flexible regions of TLL, and result in improved thermostability.
This study aimed to assess the role of prostate-specific antigen density (PSAD) and negative multiparametric magnetic resonance imaging (mpMRI) in predicting prostate cancer for biopsy-naïve men ...based on a large cohort of the Chinese population. From a prostate biopsy database between March 2017 and July 2021, we retrospectively identified 240 biopsy-naïve patients with negative prebiopsy mpMRI (Prostate Imaging Reporting and Data System version 2 PI-RADS v2 score <3). Logistic regression analysis was performed to select the potential predictors for clinically significant prostate cancer (csPCa). Receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) were performed to assess the diagnostic accuracy. The negative predictive values of mpMRI in excluding any cancer and csPCa were 83.8% (201/240) and 90.8% (218/240), respectively. ROC curve analysis indicated that PSAD was the most promising predictor, with an AUC value of 0.786 (95% confidence interval CI: 0.699-0.874), and multiparametric logistic regression analysis confirmed that higher PSAD remained a significant marker for predicting csPCa (odds ratio OR: 10.99, 95% CI: 2.75-44.02, P < 0.001). Combining negative mpMRI and PSAD below 0.20 ng ml−2 obviously increased the predictive value in excluding PCa (91.0%, 101/111) or csPCa (100.0%, 111/111). If a PSAD below 0.20 ng ml−2 was set as the criterion to omit biopsy, nearly 46.3% of patients (463 per 1000) with negative mpMRI could safely avoid unnecessary biopsy, with approximately 4.2% of patients (42 per 1000) at risk of missed diagnosis of PCa and no patients with csPCa missed. A PI-RADS v2 score <3 and a PSAD <0.20 ng ml−2 could be potential criteria for the Chinese population to omit prompt biopsy safely.
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