High-resolution flexible iontronic skins for both negative and positive pressure measurement in room temperature wind tunnel applications.

Flexible skins that can be laminated on curved surfaces are a desired form for wind pressure measurement. Sensors for such applications need to detect both negative and positive wind pressure with ultrahigh pressure resolution over a wide range up to 600 kPa, whereas existing flexible sensors are unsatisfactory to such demands. Here, we report a flexible skin containing two iontronic pressure sensors for negative pressure and positive pressure sensing, respectively, and show the potential of the skin for pressure measurement in room temperature wind tunnels. We control the contact state of iontronic interface of a sensor to introduce a pre-pressure that enables negative pressure sensing, exhibiting a pressure resolution of -20 Pa (0.025%) within a broad pressure regime (from -100 kPa to -10 Pa). The other sensor for positive pressure sensing exhibits a pressure-resolution of 100 Pa (0.025%) over 600 kPa, in addition to a wide frequency bandwidth up to 400 Hz. The skin with the two types of sensors can be attached on curved surfaces of wing surface for pressure measurement at various free stream velocities and angles of attack. This study provides a promising technology of using flexible skins for pressure measurement in aviation applications.

Metal π-Lewis base activation in palladium(0)-catalyzed trans-alkylative cyclization of alkynals.

The Pd(0)-mediated umpolung reaction of an alkyne to achieve trans-difunctionalization is a potential synthetic methodology, but its insightful activation mechanism of Pd(0)-alkyne interaction has yet to be established. Here, a Pd(0)-π-Lewis base activation mode is proposed and investigated by combining theoretical and experimental studies. In this activation mode, the Pd(0) coordinates to the alkyne group and enhances its nucleophilicity through π-back-donation, facilitating the nucleophilic attack on the aldehyde to generate a trans-Pd(ii)-vinyl complex. Ligand-effect studies reveal that the more electron-donating one would accelerate the reaction, and the cyclization of the challenging flexible C- or O-tethered substrates has been realized. The origin of regioselectivities is also explicated by the newly proposed metal π-Lewis base activation mode.

Does vertical integration increase the costs for primary care inpatients? Evidence from a national pilot programme in China.

OBJECTIVE: To assess the impact of vertical integration (VI) within County-Level Integrated Health Organisations (CIHOs) on the costs of primary care inpatients. METHODS: This study assessed Xishui, a national pilot county for CIHOs, using inpatient claims data. The treatment group comprised 10,118 inpatients from 5 vertically integrated township health centres (THCs), while the control group consisted of 21,165 inpatients from 19 non-vertically integrated THCs. The periods from July 2020 to December 2021 and January 2022 to December 2022 were defined as pre- and post-policy intervention, respectively. The primary outcome variables were total health expenditures (THS), out-of-pocket (OOP) expenditures, and the proportion of OOP expenditures. Propensity score matching was employed to align inpatient demographics and disease characteristics between the groups, followed by a difference-in-differences analysis to evaluate the outcomes. FINDINGS: VI significantly increased THS (ß = 0.1337, p < 0.01) and OOP expenditures per case (ß = 0.1661, p < 0.001), but the increase in the proportion of OOP expenditures per case was not significant (ß = 0.0029, p > 0.05). For the basic medical insurance for urban and rural residents, THS per case (ß = 0.1343, p < 0.01) and OOP expenditures (ß = 0.1714, p < 0.001) significantly increased. For the basic medical insurance system for employees, THS per case also increased significantly (ß = 0.1238, p < 0.01), but the change in OOP expenditure proportion per case was not significant (ß = 0.1020, p > 0.05). The THS per case led by Xishui County People's Hospital, the leading county medical sub-centre (CMSC), significantly increased (ß = 0.1753, p < 0.01), whereas the increase led by Xishui County Traditional Chinese Medicine Hospital was not significant (ß = 0.0742, p > 0.05). Increases in OOP expenditures per case were significant in CMSCs led by the People's Hospital and the Traditional Chinese Medicine Hospital (ß = 0.1782, p < 0.01 and ß = 0.0757, p < 0.05, respectively). CONCLUSION: VI significantly increased THS and OOP expenditures for primary care inpatients. However, VI could exacerbate economic disparities in disease burden across different insurance categories.

Palladium(0) and Brønsted Acid Co-catalyzed Enantioselective Hydro-Cyclization of 2,4-Dienyl Hydrazones and Oximes.

The transition metal-catalyzed asymmetric hydro-functionalization of 1,3-dienes has been well explored, but most reactions focus on electron-neutral substrates in an intermolecular manner. Here we first demonstrate that readily available 2,4-dienyl hydrazones and oximes can be efficiently utilized in the hydro-cyclization reaction under co-catalysis of a Brønsted acid and a chiral palladium complex, furnishing multifunctional dihydropyrazones and dihydroisoxazoles, respectively. Diverse substitution patterns for both types of electron-deficient diene compounds are tolerated, and corresponding heterocycles were generally constructed with moderate to excellent enantioselectivity, which can be elaborated to access products with higher molecular complexity and diversity. Control experiments and density functional theory calculations support that α-regioselective protonation of dienyl substrates by acid and concurrent π-Lewis base activation of Pd0 complex is energetically favoured in the formation of active π-allylpalladium intermediates, and an outer-sphere allylic amination or etherification mode is adopted to deliver the observed cyclized products enantioselectively.

Erratum to 'B4GALNT1 promotes hepatocellular carcinoma stemness and progression via integrin α2ß1-mediated FAK and AKT activation' (JHEP Reports 5 [2023] 100903).

[This corrects the article DOI: 10.1016/j.jhepr.2023.100903.].

Genome Analysis of Pseudomonas viciae G166 Conferring Antifungal Activity in Grapevine.

Grapevine (Vitis vinifera) is one of the major economic fruit crops but suffers many diseases, causing damage to the quality of grapes. Strain G166 was isolated from the rhizosphere of grapevine and was found to exhibited broad-spectrum antagonistic activities against fungal pathogens on grapes in vitro, such as Coniella diplodiella, Botrytis cinerea, and Colletotrichum gloeosporioides. Whole-genome sequencing revealed that G166 contained a 6,613,582 bp circular chromosome with 5749 predicted coding DNA sequences and an average GC content of 60.57%. TYGS analysis revealed that G166 belongs to Pseudomonas viciae. Phenotype analysis indicated that P. viciae G166 remarkably reduced the severity of grape white rot disease in the grapevine. After inoculation with C. diplodiella, more H2O2 and MDA accumulated in the leaves and resulted in decreases in the Pn and chlorophyll content. Conversely, G166-treated grapevine displayed less oxidative damage with lower H2O2 levels and MDA contents under the pathogen treatments. Subsequently, G166-treated grapevine could sustain a normal Pn and chlorophyll content. Moreover, the application of P. viciae G166 inhibited the growth of mycelia on detached leaves and berries, while more disease symptoms occurred in non-bacterized leaves and berries. Therefore, P. viciae G166 served as a powerful bioagent against grape white rot disease. Using antiSMASH prediction and genome comparisons, a relationship between non-ribosomal peptide synthase clusters and antifungal activity was found in the genome of P. viciae G166. Taken together, P. viciae G166 shows promising antifungal potential to improve fruit quality and yield in ecological agriculture.

An Adjuvanted Vaccine-Induced Pathogenesis Following Influenza Virus Infection.

An incomplete Freund's adjuvant elicited an overt pathogenesis in vaccinated mice following the intranasal challenge of A/California/07/2009 (H1N1) virus despite the induction of a higher specific antibody titer than other adjuvanted formulations. Aluminum hydroxide adjuvants have not induced any pathogenic signs in a variety of formulations with glycolipids. A glycolipid, α-galactosyl ceramide, improved a stimulatory effect of distinct adjuvanted formulations on an anti-influenza A antibody response. In contrast to α-galactosyl ceramide, its synthetic analogue C34 was antagonistic toward a stimulatory effect of an aluminum hydroxide adjuvant on a specific antibody response. The aluminum hydroxide adjuvant alone could confer complete vaccine-induced protection against mortality as well as morbidity caused by a lethal challenge of the same strain of an influenza A virus. The research results indicated that adjuvants could reshape immune responses either to improve vaccine-induced immunity or to provoke an unexpected pathogenic consequence. On the basis of these observations, this research connotes the prominence to develop a precision adjuvant for innocuous vaccination aimed at generating a protective immunity without aberrant responses.

Ultrafast piezocapacitive soft pressure sensors with over 10 kHz bandwidth via bonded microstructured interfaces.

Flexible pressure sensors can convert mechanical stimuli to electrical signals to interact with the surroundings, mimicking the functionality of the human skins. Piezocapacitive pressure sensors, a class of most widely used devices for artificial skins, however, often suffer from slow response-relaxation speed (tens of milliseconds) and thus fail to detect dynamic stimuli or high-frequency vibrations. Here, we show that the contact-separation behavior of the electrode-dielectric interface is an energy dissipation process that substantially determines the response-relaxation time of the sensors. We thus reduce the response and relaxation time to ~0.04 ms using a bonded microstructured interface that effectively diminishes interfacial friction and energy dissipation. The high response-relaxation speed allows the sensor to detect vibrations over 10 kHz, which enables not only dynamic force detection, but also acoustic applications. This sensor also shows negligible hysteresis to precisely track dynamic stimuli. Our work opens a path that can substantially promote the response-relaxation speed of piezocapacitive pressure sensors into submillisecond range and extend their applications in acoustic range.

Palladium(0) π-Lewis Base Catalysis: Concept and Development.

The development of a new catalytic strategy plays a vital role in modern organic chemistry since it permits bond formation in an unprecedented and more efficient manner. Although the application of preformed metal complexes as π-base-activated reagents have enabled diverse transformations elegantly, the concept and strategy by directly utilizing transition metals as efficient π-Lewis base catalysts remain underdeveloped, especially in the field of asymmetric catalysis. Here, we outline our perspective on the discovery of palladium(0) as an efficient π-Lewis base catalyst, which is capable of increasing the highest occupied molecular orbital (HOMO) energy of both electron-neutral and electron-deficient 1,3-dienes and 1,3-enynes upon flexible η2-complexes formed in situ and resultant π-backdonation. Thus, fruitful carbon-carbon-forming reactions with diverse electrophiles can be achieved enantioselectively in a vinylogous addition pattern, which is conceptually different from the classical oxidative cyclization mechanism. Emphasis will be given to the concept and mechanism elucidation, catalytic features, and reaction design together with perspective on the further development of this emerging field.

Pd(0)-Catalyzed Asymmetric Cyclization/Coupling Cascade of Alkyne-Tethered Unsaturated Carbonyls: Development and Mechanism Elucidation.

While the Pd(0)-catalyzed cyclization of alkyne-tethered unsaturated carbonyl substrates has been reported, the mechanism has not been well elucidated, and the potential asymmetric version remains to be developed. Here, we disclose that a chiral Pd(0) complex can efficiently promote the desymmetrizative cyclization of alkyne-tethered cyclohexadienones in CH3OH, and the resultant Pd(II) intermediates further undergo an array of tandem coupling reactions, including Suzuki, Sonogashira, and even chemoselective reduction by CH3OH in the absence of additional coupling partners. As a result, a broad spectrum of hydrobenzofuran derivatives, having a tetra- or trisubstituted exo-alkene motif, is constructed with moderate to outstanding enantioselectivity in an exclusive cis-difunctionalization pattern. In addition, this enantioselective protocol can be well expanded to linear alkyne-tethered unsaturated carbonyls, and a new desymmetrizative and asymmetric cyclization/coupling cascade of bis-alkyne-tethered enones is further realized efficiently, furnishing diversely structured frameworks with high stereoselectivity. Moreover, kinetic transformation for various racemic alkyne-tethered enones can be accomplished under similar catalytic conditions, and unusual kinetic reactions by chemoselectively undertaking Suzuki or Sonogashira coupling, or reduction by CH3OH, occur sequentially, finally yielding two types of chiral products, both with high enantioselectivity via either ligand- or substrate-based control. The experimental results demonstrate that the current Pd(0)-based strategy is superior to the classical Pd(II)-catalyzed carbopalladation/cyclization process of the identical substrates with regard to enantioselectivity and synthetic versatility. Moreover, density functional theory calculations are conducted to rationalize the Pd(0)-catalyzed oxidative cyclometalation pathway in the key cyclization step, which leads to the observed cis-difunctionalized products exclusively.

Functional-Group-Directed Regiodivergent (3 + 2) Annulations of Electronically Distinct 1,3-Dienes and 2-Formyl Arylboronic Acids.

Presented herein is a palladium-catalyzed asymmetric (3 + 2) annulation reaction between 1,3-dienes and 2-formylarylboronic acids, proceeding in a cascade vinylogous addition and Suzuki coupling process. Both electron-neutral and electron-deficient 1,3-dienes are compatible under similar catalytic conditions, and distinct regioselectivity is observed via functional-group control of 1,3-diene substrates. A collection of 1-indanols with dense functionalities is constructed stereoselectively.

Ultraviolet-Visible-Near Infrared Spectroscopy May Aid in the Qualitative Assessment of Early-Stage Cartilage Degradation.

Purpose: To assess the potential of ultraviolet-visible near-infrared spectroscopy to provide quantitative information on the cartilage surface at early osteoarthritis. Methods: We used a similar source and optical path to a standard arthroscope and constraining input to the range available to a standard detector/camera, further capturing and analyzing spectral information quantitatively in terms of specific electronic absorbance bands and scattering from the cartilage surface, with a focus on the early stages of degradation. Results: The ratio of the 320-nm and longer than 500-nm absorbances produced a distinct change from the normal to diseased states. The slopes between the wavelengths of 600 and 980 nm may show the transition of the single fibril to fibril bundles that occurs during early stages disease. Conclusions: Ultraviolet-visible near-infrared spectroscopy has good potential for use in integrated arthroscopic assessment. Clinical Relevance: This raises the possibility of advancing arthroscopy from a qualitative to a quantitative tool, without requiring modification of either the radiation (the light source and path) or instrumentation (the arthroscope itself) delivered to the patient, thus allowing a low-cost yet potentially high-value technology.

Two-dimensional MXene Nanomaterials: Preparation, Structure Modulation and the Applications in Electrochemical Energy Storage.

BACKGROUND: MXenes have attracted intensive attention owing to their unique twodimensional (2D) layered structure, high specific surface area, excellent conductivity, superior surface hydrophilicity, and chemical stability. In recent years, selective etching of the A element layers from MAX phases by fluorine-containing etchants (HF, LiF-HCl, etc) is a common method to prepare multilayered MXene nanomaterials (NMs) with plentiful surface terminations. At present, many studies have been reported on the use of fluorine-free etchants (NaOH, ZnCl2, etc) to etch MAX phases. The properties of MXene NMs are dependent on their structures. OBJECTIVE: The purpose of this review is to focus on a comprehensive and systematical survey on the preparation, structure modulation, and applications of MXene NMs in electrochemical energy storage devices, including supercapacitors, lithium-ion battery, sodium-ion battery, potassium-ion battery, and aluminum-ion battery. METHODS: Extensive information related to the preparation and applications of 2D MXene NMs for electrochemical energy storage and their associated patents were collected. This review highlights the recently reported 2D MXene NMs which are used in supercapacitor and various metal ion. RESULTS: It is found that the preparation methods have great impacts on the layer spacing and surface terminations of MXenes, consequently affecting their performance. Hence, this paper summarizes the research progress of the preparation strategies, layer spacing and surface termination modulation of MXene NMs. CONCLUSION: The applications of 2D MXene NMs in electrochemical energy storage are outlined. The forward-looking challenges and prospects for the development of MXenes are also proposed.

Nanocrystal Materials for Resistive Memory and Artificial Synapses: Progress and Prospects.

BACKGROUND: Resistive random-access memory (RRAM) is considered to be the most promising next-generation non-volatile memory because of its low cost, low energy consumption, and excellent data storage characteristics. However, the on/off (SET/RESET) voltages of RRAM are too random to replace the traditional memory. Nanocrystals (NCs) offer an appealing option for these applications since they combine excellent electronic/optical properties and structural stability and can address the requirements of low-cost, large-area, and solution-processed technologies. Therefore, the doping NCs in the function layer of RRAM are proposed to localize the electric field and guide conductance filaments (CFs) growth. OBJECTIVE: The purpose of this article is to focus on a comprehensive and systematical survey of the NC materials, which are used to improve the performance of resistive memory (RM) and optoelectronic synaptic devices and review recent experimental advances in NC-based neuromorphic devices from artificial synapses to light-sensory synaptic platforms. METHODS: Extensive information related to NCs for RRAM and artificial synapses and their associated patents were collected. This review aimed to highlight the unique electrical and optical features of metal and semiconductor NCs for designing future RRAM and artificial synapses. RESULTS: It was demonstrated that doping NCs in the function layer of RRAM could not only improve the homogeneity of SET/RESET voltage but also reduce the threshold voltage. At the same time, it could still increase the retention time and provide the probability of mimicking the bio-synapse. CONCLUSION: NC doping can significantly enhance the overall performance of RM devices, but there are still many problems to be solved. This review highlights the relevance of NCs for RM and artificial synapses and also provides a perspective on the opportunities, challenges, and potential future directions.

CTCF modulates adipocyte lipolysis via directly regulating the expression of Beclin 1 with the cooperation of PPARγ.

Dysregulated lipolysis is a risk factor contributing to metabolic diseases and autophagy is known to be important in lipolysis. CTCF is involved in diverse cellular processes including adipogenesis, yet its role in lipolysis or autophagy remains unknown. We identified lipolytic genes were downregulated in CTCF knockdown adipocytes based on the RNA-seq data. Further validation showed that CTCF knockdown restrained adipocyte lipolysis while overexpression of CTCF had opposite effects. Similarly, overexpression and knockdown studies demonstrated that CTCF was a positive regulator of autophagy. Treatment with autophagy inducer relieved the suppression of lipolysis caused by CTCF knockdown, while autophagy inhibitor treatment alleviated lipolysis stimulated by CTCF overexpression, indicating that CTCF regulates adipocyte lipolysis through autophagy. Mechanistically, CTCF interacted with PPARγ to coordinately enhanced lipolytic capacity. Data of chip-seq, chip-qPCR and further experiments confirmed that CTCF and PPARγ separately stimulated transactivation of autophagy regulatory protein Beclin 1, while co-expression of the two displayed synergistic effects to regulate autophagy flux. Expectedly, overexpression of Beclin 1 abolished the blockage of lipolysis and autophagy caused by CTCF knockdown. Collectively, CTCF cooperates with PPARγ to regulate autophagy via directly modulating BECLIN 1 transcription, thereby leading to increased adipocyte lipolysis.

Enantioselective Construction of Eight-Membered N-Heterocycles from Simple 1,3-Dienes via Pd(0) Lewis Base Catalysis.

We report herein an unprecedented enantioselective (4+4) cycloaddition of simple 1,3-dienes with azadienes for the construction of fused eight-membered N-heterocycles. In this transformation, the π-Lewis basic Pd(0) catalyst achieves activation of 1,3-dienes to induce nucleophilic addition to azadienes followed by ring cyclization via a selective terminal allylic substitution. Furthermore, highly efficient and diastereoselective derivatizations of the eight-membered rings provide a facile access to diverse enantiopure fused tetra- to hexacyclic compounds with potential application in medicinal chemistry.

Risk factors and predictive models for early recurrent intussusception in children: a retrospective cohort study.

Background: Early recurrent intussusception (ERI) in children is common and seriously affects the physical and mental health of the children. There are few reports discussing risk factors for ERI in children, and this study aims to identify risk factors for ERI in children and build predictive models. Methods: We conducted a retrospective study of 787 children with no relapse intussusception (NRI) and 82 children with ERI between January 2011 and December 2021. Univariate and multifactorial stepwise logistic regression analysis was used to analyze the correlation between 11 factors and ERI, to determine the independent risk factors for ERI in children. The prediction model was established by independent risk factors and then verified. Results: Age, vomiting, bloody stools, and monocyte ratios were independently correlated with the composite endpoint (P<0.05). A nomogram was constructed and a calibration curve was plotted, using independent risk factors. Based on the disease's diagnostic score, the predictive model's performance was validated by using logistic regression receiver operating characteristic (ROC) curve detection, with area under the curve (AUC) value of 0.883 [95% confidence interval (CI): 0.846-0.920], and the calibration curve was close to the ideal diagonal line. In addition, the decision curve analysis (DCA) showed that the model had significant net benefits. Conclusions: Independent risk factors for ERI in children are age, vomiting, bloody stool, and monocyte ratio. Children older than 1 year in age, who lacked vomiting and bloody stool symptoms, and who exhibited an elevated ratio of monocytes were more likely to relapse early. The predictive model constructed herein can predict the early recurrence of children with ERI, providing a reference for clinicians' individualized judgments.

Palladium(0)-Catalyzed Enantioselective Construction of Multifunctional Piperidine Derivatives from 1,3-Dienes, N-Cyano Imines, and Beyond.

An enantioselective (4 + 2) reaction between 1,3-dienes and N-cyano imines has been developed under Pd(0) catalysis, proceeding through a cascade vinylogous addition and intramolecular allylic amination sequence. 2,6-cis-Disubstituted-1,2,3,6-tetrahydropyridines were furnished as single diastereomers in moderate to good yields and enantiocontrol. Moreover, a more challenging three-component (2 + 2 + 2) annulation of 1,3-dienes, N-cyano imines, and activated alkenes was efficiently realized to afford piperidines with high structural complexity, albeit with moderate enantioselectivity.

B4GALNT1 promotes hepatocellular carcinoma stemness and progression via integrin α2ß1-mediated FAK and AKT activation.

Background & Aims: ß-1,4-N-Acetyl-galactosaminyltransferase 1 (B4GALNT1) has been reported to contribute to the development of human malignancies. However, its role in hepatocellular carcinoma (HCC) remains uncharacterised. In this study, we aimed to elucidate the role of B4GALNT1 in HCC stemness and progression. Methods: Immunohistochemical staining was used to evaluate B4GALNT1 expression in HCC tissues and adjacent normal liver tissues. Flow cytometry analysis and sphere formation analysis were performed to investigate the role of B4GALNT1 in HCC stemness. Colony formation, Incucyte, wound-healing, Transwell migration, and invasion assays, and an animal model were used to study the role of B4GALNT1 in HCC progression. RNA-sequencing and co-immunoprecipitation were used to investigate the downstream targets of B4GALNT1. Results: B4GALNT1 was upregulated in HCC and associated with poor clinical outcome of patients with the disease. Moreover, B4GALNT1 promoted HCC stemness, migration, invasion, and growth. Mechanistically, B4GALNT1 not only promoted the expression of the integrin α2ß1 ligand THBS4, but also directly interacted with the ß subunit of integrin α2ß1 ITGB1 to inhibit its ubiquitin-independent proteasomal degradation, resulting in activation of FAK and AKT. Ophiopogonin D inhibited HCC stemness and progression by reducing ITGB1 and THBS4 expression and inhibiting FAK and AKT activation. Conclusions: Our study suggests the B4GALNT1/integrin α2ß1/FAK/PI3K/AKT axis as a therapeutic target for the inhibition of HCC stemness and tumour progression. Impact and implications: The role and regulatory mechanism of B4GALNT1 in HCC have not been studied previously. Here, we reveal that B4GALNT1 has a crucial role in HCC stemness and progression by activating the integrin α2ß1/FAK/PI3K/AKT axis, providing a potential target for HCC therapy. In addition, we find Ophiopogonin D as a potential therapeutic drug for patients with HCC.

Mapping the scientific research on integrated care: a bibliometric and social network analysis.

Background: Integrated care (IC) is the cornerstone of the sustainable development of the medical and health system. A thorough examination of the existing scientific literature on IC is essential for assessing the present state of knowledge on this subject. This review seeks to offer an overview of evidence-based knowledge, pinpoint existing knowledge gaps related to IC, and identify areas requiring further research. Methods: Data were retrieved from the Web of Science Core Collection, from 2010 to 2020. Bibliometrics and social network analysis were used to explore and map the knowledge structure, research hotspots, development status, academic groups and future development trends of IC. Results: A total of 7,501 articles were obtained. The number of publications on IC was rising in general. Healthcare science services were the most common topics. The United States contributed the highest number of articles. The level of collaboration between countries and between authors was found to be relatively low. The keywords were stratified into four clusters: IC, depression, integrative medicine, and primary health care. In recent years, complementary medicine has become a hotspot and will continue to be a focus. Conclusion: The study provides a comprehensive analysis of global research hotspots and trends in IC, and highlights the characteristics, challenges, and potential solutions of IC. To address resource fragmentation, collaboration difficulties, insufficient financial incentives, and poor information sharing, international collaboration needs to be strengthened to promote value co-creation and model innovation in IC. The contribution of this study lies in enhancing people's understanding of the current state of IC research, guiding scholars to discover new research perspectives, and providing valuable references for researchers and policymakers in designing and implementing effective IC strategies.