Gaps between current practice in perinatal depression screening and guideline recommendations: a systematic review.

OBJECTIVE: Screening for perinatal depression is recommended by many guidelines to reduce the disease burden, but current implementation practices require clarification. METHOD: Fifteen databases were searched for observational studies using a pre-tested search strategy. In addition, the websites of academic organizations were searched for guidelines, recommendations, and reports. Literature published between January 1, 2010, and December 19, 2021, in either English or Chinese, was included. The standard form of the Joanna Briggs Institute (JBI) was used to assess risk of bias of the included studies. RESULTS: The data analysis covered 103 studies, 21 guidelines, 11 recommendations, five position statements, three reports, two committee opinions, three consensuses, one consultation, and one policy statement. All but one guideline recommended that mothers be routinely screened for perinatal depression at least once during the perinatal period. In addition, 39 documents recommended that perinatal mothers at risk of perinatal depression be provided with or referred to counseling services. In original studies, however, only 8.7% of the original studies conducted routine screenings, and only one-third offered referral services after the screening process. The EPDS emerged as the most frequently used screening tool to measure perinatal depression. 32% (n = 33) of studies reported the technology used for screening. The most commonly used method was face-to-face interviews (n = 22). Screening personnel the agents conducting the screening comprised researchers (n = 26), nurses (n = 15), doctors (n = 11). CONCLUSIONS: A significant disparity was observed between the recommendations and implementation of perinatal depression screening, highlighting the need to integrate routine screening and referral processes into maternal care services.

Changes of Nitrate Activity and Byproduct Distribution Characteristics for Synergistic NOx and Dioxin Abatement over V2O5/AC Catalyst.

The simultaneous removal of NOx and dioxins has been considered an economical and effective technology of controlling multipollutant flue gas in the context of "carbon peaking and carbon neutrality". However, this technology has not yet been implemented in practical situations, because the interactive relationship between the selective catalytic reduction (SCR) reaction and dioxin catalytic oxidation lacks a deep understanding, especially on a carbon-based catalyst. In this research, the influence of NO and NH3 on the oxidation characteristics and byproducts distribution of dibenzofuran (DBF) was studied on V2O5/AC catalyst. Results indicated that NH3 has a stronger inhibition effect for DBF catalytic oxidation than NO due to obvious competitive adsorption between NH3 and DBF on the V2O5/AC catalyst. In addition, although both NO and NH3 inhibit the complete degradation of DBF, their effects on the byproduct distribution are not consistent. NO primarily affects the level of oxygen-containing byproducts, while NH3 primarily affects the level of alkane byproducts. Furthermore, the SCR reaction activity demonstrated a reduction when DBF was present. The occupation of V2O5 sites by DBF and its oxidizing intermediates has hindered the production of monodentate nitrate and the reactivity of bridged nitrate, resulting in a decrease in SCR activity via the L-H mechanism. This work aims to provide theoretical guidance for simultaneous removal of NOx and dioxins in industrial fumes.

Association of serum creatinine to cystatin C to waist circumference ratios and hypertension: evidence from China health and retirement longitudinal study.

Background: The objective of this study was to explore the association between the ratio of serum creatinine to cystatin C to waist circumference (CCR/WC) and hypertension. Methods: The study utilized data extracted from the China Health and Retirement Longitudinal Study. In the cross-sectional analysis, logistic regression analyses were employed to examine the association between the CCR/WC ratio and hypertension. By utilizing restricted cubic splines, potential non-linear associations between the CCR/WC ratio and hypertension were explored. In the longitudinal analysis, the association between CCR/WC quartiles (Q1-Q4) and the risk of new-onset hypertension was evaluated by Cox proportional-hazards models. Results: In total, 7,253 participants were enrolled. The study unveiled an inverse association with hypertension, demonstrating an odds ratio (OR) of 0.29 (95% confidence interval [CI]: 0.23-0.37, P < 0.001). Among males, an OR of 0.38 (95% CI: 0.25-0.58, P < 0.001) was observed, while among females, an OR of 0.41 (95% CI: 0.28-0.60, P < 0.001) was noted. There was an absence of a nonlinear association between the CCR/WC ratio and hypertension. Cox regression analysis unveiled a reduced risk of hypertension in Q3 (Hazard ratios [HR]: 0.69, 95% CI: 0.58-0.82, P < 0.001) and Q4: (HR: 0.70, 95% CI: 0.59-0.83, P < 0.001) in compared to the Q1 of the CCR/WC ratio, and sex-specific analysis yielded consistent results. Conclusion: This study emphasizes the potential association between an elevated CCR/WC ratio and a reduced risk of hypertension.

Inferred drought-induced plant allocation shifts and their impact on drought legacy at a tropical forest site.

While droughts predominantly induce immediate reductions in plant carbon uptake, they can also exert long-lasting effects on carbon fluxes through associated changes in leaf area, soil carbon, etc. Among other mechanisms, shifts in carbon allocation due to water stress can contribute to the legacy effects of drought on carbon fluxes. However, the magnitude and impact of these allocation shifts on carbon fluxes and pools remain poorly understood. Using data from a wet tropical flux tower site in French Guiana, we demonstrate that drought-induced carbon allocation shifts can be reliably inferred by assimilating Net Biosphere Exchange (NBE) and other observations within the CARbon DAta MOdel fraMework. This model-data fusion system allows inference of optimized carbon and water cycle parameters and states from multiple observational data streams. We then examined how these inferred shifts affected the duration and magnitude of drought's impact on NBE during and after the extreme event. Compared to a static allocation scheme analogous to those typically implemented in land surface models, dynamic allocation reduced average carbon uptake during drought recovery by a factor of 2.8. Additionally, the dynamic model extended the average recovery time by 5 months. The inferred allocation shifts influenced the post-drought period by altering foliage and fine root pools, which in turn modulated gross primary productivity and heterotrophic respiration for up to a decade. These changes can create a bust-boom cycle where carbon uptake is enhanced some years after a drought, compared to what would have occurred under drought-free conditions. Overall, allocation shifts accounted for 65% [45%-75%] of drought legacy effects in modeled NBE. In summary, drought-induced carbon allocation shifts can play a substantial role in the enduring influence of drought on cumulative land-atmosphere CO2 exchanges and should be accounted for in ecosystem models.

Minor Hydroxylated Triterpenoids Produced in Engineered Yeast by the Enzymes OSC and CYP716s from the Plant Enkianthus chinensis and Their Anti-Inflammatory and Hepatoprotective Activities.

Triterpenoids are a type of specialized metabolites that exhibit a wide range of biological activities. However, the availability of some minor triterpenoids in nature is limited, which has hindered our understanding of their pharmacological potential. To overcome this limitation, heterologous biosynthesis of triterpenoids in yeast has emerged as a promising and time-efficient production platform for obtaining these minor compounds. In this study, we analyzed the transcriptomic data of Enkianthus chinensis to identify one oxidosqualene cyclase (EcOSC) gene and four CYP716s. Through heterologous expression of these genes in yeast, nine natural pentacyclic triterpenoids, including three skeleton products (1-3) produced by one multifunctional OSC and six minor oxidation products (4-9) catalyzed by CYP716s, were obtained. Of note, we discovered that CYP716E60 could oxidize ursane-type and oleanane-type triterpenoids to produce 6ß-OH derivatives, marking the first confirmed C-6ß hydroxylation in an ursuane-type triterpenoid. Compound 9 showed moderate inhibitory activity against NO production and dose-dependently reduced IL-1ß and IL-6 production at the transcriptional and protein levels. Compounds 1, 2, 8, and 9 exhibited moderate hepatoprotective activity with the survival rates of HepG2 cells from 61% to 68% at 10 µM.

Design, Synthesis, and Biological Evaluation of Novel Cinnamide Derivatives as Neuroprotective Agents for the Treatment of Cerebral Ischemia.

BACKGROUND: Ischemic stroke, the most common type of cerebrovascular accident, is a major cause of severe disability among adults worldwide. Although there has been progress in interventions for ischemic stroke in the past decades, there is no effective treatment to prevent brain damage in acute ischemic stroke. Therefore, it is urgent to develop novel neuroprotective agents with a wide therapeutic time window to provide a better prognosis for ischemic stroke patients. OBJECTIVE: The current study aimed to synthesize novel derivatives with substituent cinnamide scaffolds, evaluate biological activity, and obtain neuroprotective agents. METHODS: The target compounds were synthesized using classical methods of medicinal chemistry. The neuroprotective effects in vitro against Glu-induced neurotoxicity injury were evaluated in PC12 cells by MTT assay. The cell apoptosis was analyzed by flow cytometer. The proteins were detected by western blotting. The neuroprotective activities in vivo were determined in two in vivo models of global and focal cerebral ischemia. RESULTS: Among the title compounds, 9t, 9u, 9y, and 9z exhibited good neuroprotection in vivo and in vitro, which were selected and further studied to determine their mechanism of action. 9t, 9u, 9y and 9z protected PC12 cells against glutamate-induced apoptosis in a dose-dependent manner via caspase-3 pathway. Moreover, the four compounds significantly reduced brain infarct area and exhibited excellent neuroprotective activities in the in vivo MCAO model. CONCLUSION: Compounds 9t, 9u, 9y, and 9z, as potent neuroprotective agents with anti- neurotoxicity activity in vitro and anticerebral infarction efficacy in vivo, might serve as a useful molecular tool for further physiology and pathophysiology function studies, leading to potential clinical therapeutic agents for ischemic injury.

[Study on changes of Styrax varieties].

Styrax is a commonly used imported traditional Chinese medicinal material in China. It was introduced to China in the Han Dynasty and was first described as a traditional Chinese medicine in Miscellaneous Records of Famous Physicians(Ming Yi Bie Lu). In this paper, by combing ancient and modern Chinese and foreign herbal medicine books and modern literature, combined with the results of field investigations on the origin of Styrax, the changes of Styrax involving the name, quality evaluation, origin, place of origin, and harvesting and processing were systematically verified. The results show that since ancient times, the origin and place of origin of Styrax have been unclear. The medical scientists of all dynasties in China have evaluated the quality of Styrax from four aspects: texture, viscosity, odor concentration, and color. The varieties of Styrax changed twice. The first change may have occurred during the Sui and Tang Dynasties, and the base changed from Styrax officinalis to Liquidambar orientalis. The second change was in modern times, and the base changed from L. orientalis to L. styraciflua. At the same time, the place of origin changed for the first time, from Turkey, Syria, and other countries in southern Asia Minor to Honduras, Guatemala, and other countries in Central America and southern North America. This paper studied the historical evolution of Styrax in terms of quality evaluation, origin, place of origin, character, and harvesting and processing. At the same time, it summarized the application of Styrax in the western countries, which can provide a historical basis for the further development and utilization of Styrax.

Robust Tensor-Based DOA and Polarization Estimation in Conformal Polarization Sensitive Array with Bad Data.

Partially impaired sensor arrays pose a significant challenge in accurately estimating signal parameters. The occurrence of bad data is highly probable, resulting in random loss of source information and substantial performance degradation in parameter estimation. In this paper, a tensor variational sparse Bayesian learning (TVSBL) method is proposed for the estimate of direction of arrival (DOA) and polarization parameters jointly based on a conformal polarization sensitive array (CPSA), taking into account scenarios with the partially impaired sensor array. First, a sparse tensor-based received data model is developed for CPSAs that incorporates bad data. Then, a column vector detection method is proposed to diagnose the positions of the impaired sensors. In scenarios involving partially impaired sensor arrays, a low-rank matrix completion method is employed to recover the random loss of signal information. Finally, variational sparse Bayesian learning (VSBL) and minimum eigenvector methods are utilized sequentially to obtain the DOA and polarization parameters estimation, successively. Furthermore, the Cramér-Rao bound is given for the proposed method. Simulation results validated the effectiveness of the proposed method.

Hydrogel loaded with thiolated chitosan modified taxifolin liposome promotes osteoblast proliferation and regulates Wnt signaling pathway to repair rat skull defects.

To alleviate skull defects and enhance the biological activity of taxifolin, this study utilized the thin-film dispersion method to prepare paclitaxel liposomes (TL). Thiolated chitosan (CSSH)-modified TL (CTL) was synthesized through charge interactions. Injectable hydrogels (BLG) were then prepared as hydrogel scaffolds loaded with TAX (TG), TL (TLG), and CTL (CTLG) using a Schiff base reaction involving oxidized dextran and carboxymethyl chitosan. The study investigated the bone reparative properties of CTLG through molecular docking, western blot techniques, and transcriptome analysis. The particle sizes of CTL were measured at 248.90 ± 14.03 nm, respectively, with zeta potentials of +36.68 ± 5.43 mV, respectively. CTLG showed excellent antioxidant capacity in vitro. It also has a good inhibitory effect on Escherichia coli and Staphylococcus aureus, with inhibition rates of 93.88 ± 1.59 % and 88.56 ± 2.83 % respectively. The results of 5-ethynyl-2 '-deoxyuridine staining, alkaline phosphatase staining and alizarin red staining showed that CTLG also had the potential to promote the proliferation and differentiation of mouse embryonic osteoblasts (MC3T3-E1). The study revealed that CTLG enhances the expression of osteogenic proteins by regulating the Wnt signaling pathway, shedding light on the potential application of TAX and bone regeneration mechanisms.

Synthesis of Taxifolin-Loaded Polydopamine for Chemo-Photothermal-Synergistic Therapy of Ovarian Cancer.

Chemotherapy is a well-established method for treating cancer, but it has limited effectiveness due to its high dosage and harmful side effects. To address this issue, researchers have explored the use of photothermal agent nanoparticles as carriers for precise drug release in vivo. In this study, three different sizes of polydopamine nanoparticles (PDA-1, PDA-2, and PDA-3) were synthesized and evaluated. PDA-2 was selected for its optimal size, encapsulation rate, and drug loading rate. The release of the drug from PDA-2@TAX was tested at different pH and NIR laser irradiation levels. The results showed that PDA-2@TAX released more readily in an acidic environment and exhibited a high photothermal conversion efficiency when exposed to an 808 nm laser. In vitro experiments on ovarian cancer cells demonstrated that PDA-2@TAX effectively inhibited cell proliferation, highlighting its potential for synergistic chemotherapy-photothermal treatment.

Revisiting the relationships between energy consumption, economic development and urban size: A global perspective using remote sensing data.

Existing methods of measuring energy consumption require complex statistics and computing. A real-time and globally applicable approach for comparing energy consumption across different cities is still lacking. Additionally, the nonlinear relationships and varying thresholds of energy consumption in relation to economic activities and urbanization remain unconfirmed. This study aims to fill these gaps by utilizing Suomi National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (NPP-VIIRS) nighttime light data in 2015 and a top-down approach based on a multiple regression model to examine energy consumption in global cities employing a redefined urban boundary. It also explores the accurate relationship between energy consumption, population density (as a proxy of urbanization), and per capita gross domestic product (GDP) across different regions and urban sizes using generalized additive models and regression models. High-resolution gridded population and GDP datasets covering the entire planet are utilized for this purpose. The study also estimates the development potentiality. The study yields followings outcomes: Firstly, the top 30 cities with the highest per capita energy consumption account for over 0.66% of the total per capita energy consumption of all cities. Secondly, in East Asia (EA) and Southeast Asia (SEA), the per capita energy consumption decreases when per capita GDP reaches $40,000 and $75,000, respectively, while it remains stable in cities located in Western Europe (WE) and North America (NA) as per capita GDP increases. Thirdly, the per capita energy consumption declines with increasing urban population density until reaching 10,000 person/km2, 22,000 person/km2, and 4000 person/km2 in EA, SEA, and NA, respectively. Fourthly, in Central Asia (CA), megacities can save over 100 Mbtu/population when per capita GDP increases by $1000 compared to big cities. This pioneering study provides a comparable investigation of energy consumption at the global city level, exploring its relationship with urbanization and economy by employing a unified calculation standard. It will facilitate long-term energy-saving policies and urban planning strategies.

Dopamine-grafted oxidized hyaluronic acid/gelatin/cordycepin nanofiber membranes modulate the TLR4/NF-kB signaling pathway to promote diabetic wound healing.

Due to impaired immune function, diabetic wounds are highly susceptible to the development of excessive inflammatory responses and prolonged recurrent bacterial infections that impede diabetic wound healing. Therefore, it is necessary to design and develop a wound dressing that controls bacterial infection and inhibits excessive inflammatory response. In this study, hyaluronic acid (HA) was modified using dopamine (DA). Subsequently, cordycepin (COR) was loaded into dopamine-modified hyaluronic acid (OHDA)/gelatin (GEL) nanofiber wound dressing by electrostatic spinning technique. The constructed COR/OHDA/GEL nanofiber membrane has good thermal stability, hydrophilicity, and air permeability. In vitro experiments showed that the obtained COR/OHDA/GEL nanofiber membranes had good antimicrobial efficacy (S. aureus: 95.60 ± 0.99 %, E. coli: 71.17 ± 6.87 %), antioxidant activity (>90 %), and biocompatibility. In vivo experiments showed that COR/OHDA/GEL nanofiber membranes could promote wound tissue remodeling, collagen deposition, and granulation tissue regeneration. Western blot experiments showed that COR/OHDA/GEL nanofibrous membranes could inhibit the excessive inflammatory response of wounds through the TLR4/NF-κB signaling pathway. Therefore, COR/OHDA/GEL nanofiber membranes could promote diabetic wound healing by modulating the inflammatory response. The results showed that the designed nanofiber wound dressing is expected to provide a new strategy for treating chronic wounds.

Highly sensitive detection of multiple antiviral drugs using graphitized hydroxylated multi-walled carbon nanotubes/ionic liquids-based electrochemical sensors.

Global outbreaks and the spread of viral diseases in the recent years have led to a rapid increase in the usage of antiviral drugs (ATVs), the residues and metabolites of which are discharged into the natural environment, posing a serious threat to human health. There is an urgent need to develop sensitive and rapid detection tools for multiple ATVs. In this study, we developed a highly sensitive electrochemical sensor comprising a glassy carbon electrode (GCE) modified with graphitized hydroxylated multi-walled carbon nanotubes (G-MWCNT-OH) and 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6, IL) for the detection of six ATVs including famciclovir (FCV), remdesivir (REM), favipiravir (FAV), hydroxychloroquine sulfate (HCQ), cepharanthine (CEP) and molnupiravir (MOL). The morphology and structure of the G-MWCNT-OH/IL nanocomposites were characterized comprehensively, and the electroactive surface area and electron conductivity of G-MWCNT-OH/IL/GCE were determined using cyclic voltammetry and electrochemical impedance spectroscopy. The thermodynamic stability and non-covalent interactions between the G-MWCNT-OH and IL were evaluated through quantum chemical simulation calculations, and the mechanism of ATV detection using the G-MWCNT-OH/IL/GCE was thoroughly examined. The detection conditions were optimized to improve the sensitivity and stability of electrochemical sensors. Under the optimal experimental conditions, the G-MWCNT-OH/IL/GCE exhibited excellent electrocatalytic performance and detected the ATVs over a wide concentration range (0.01-120 µM). The limit of detections (LODs) were 42.3 nM, 55.4 nM, 21.9 nM, 15.6 nM, 10.6 nM, and 3.2 nM for FCV, REM, FAV, HCQ, CEP, and MOL, respectively. G-MWCNT-OH/IL/GCE was also highly stable and selective to the ATVs in the presence of multiple interfering analytes. This sensor exhibited great potential for enabling the quantitative detection of multiple ATVs in actual water environment.

New species and new record of Statherotmantis Diakonoff, 1973 from China (Lepidoptera: Tortricidae: Olethreutinae).

In China, six species of Statherotmantis Diakonoff, 1973 were previously recorded. In the present study, four other species were recognized using morphology and DNA barcording analysis. Among these, three of which, S. miniscula sp. n., S. calva sp. n., and S. longiuscula sp. n., are described as new. In addition, one species, S. laetana Kuznetzov, 1988, is a new record for China. Adults and genitalia are illustrated, and keys to identify the Chinese species of Statherotmantis are provided.

Epithelioid hemangioendothelioma (EHE) with WWTR1::TFE3 gene fusion, a novel fusion variant.

Epithelioid hemangioendothelioma (EHE) is a rare endothelial sarcoma associated with a high incidence of metastases and for which there are no standard treatment options. Based on disease-defining mutations, most EHEs are classified into two subtypes: WWTR1::CAMTA1-fused EHE or YAP1::TFE3-fused EHE. However, rare non-canonical fusions have been identified in clinical samples of EHE cases and are challenging to classify. In this study, we report the identification of a novel WWTR1::TFE3 fusion variant in an EHE patient using targeted RNA sequencing. Histologically, the tumor exhibited hybrid morphological characteristics between WWTR1::CAMTA1-fused EHE and YAP1::TFE3-fused EHE. In addition to the driver fusion, there were six additional secondary mutations identified, including a loss-of-function FANCA mutation. Furthermore, in vitro studies were conducted to investigate the tumorigenic function of the WWTR1::TFE3 fusion protein in NIH3T3 cells and demonstrated that WWTR1::TFE3 promotes colony formation in soft agar. Finally, as the wild-type WWTR1 protein relies on binding the TEAD family of transcription factors to affect gene transcription, mutation of the WWTR1 domain of the fusion protein to inhibit such binding abrogates the transformative effect of WWTR1::TFE3. Overall, we describe a novel gene fusion in EHE with a hybrid histological appearance between the two major genetic subtypes of EHE. Further cases of this very rare subtype of EHE will need to be identified to fully elucidate the clinical and pathological characteristics of this unusual subtype of EHE.

Characterization and Engineering of Two Highly Paralogous Sesquiterpene Synthases Reveal a Regioselective Reprotonation Switch.

Sesquiterpene synthases (STPSs) catalyze carbocation-driven cyclization reactions that can generate structurally diverse hydrocarbons. The deprotonation-reprotonation process is widely used in STPSs to promote structural diversity, largely attributable to the distinct regio/stereoselective reprotonations. However, the molecular basis for reprotonation regioselectivity remains largely understudied. Herein, we analyzed two highly paralogous STPSs, Artabotrys hexapetalus (-)-cyperene synthase (AhCS) and ishwarane synthase (AhIS), which catalyze reactions that are distinct from the regioselective protonation of germacrene A (GA), resulting in distinct skeletons of 5/5/6 tricyclic (-)-cyperene and 6/6/5/3 tetracyclic ishwarane, respectively. Isotopic labeling experiments demonstrated that these protonations occur at C3 and C6 of GA in AhCS and AhIS, respectively. The cryo-electron microscopy-derived AhCS complex structure provided the structural basis for identifying different key active site residues that may govern their functional disparity. The structure-guided mutagenesis of these residues resulted in successful functional interconversion between AhCS and AhIS, thus targeting the three active site residues [L311-S419-C458]/[M311-V419-A458] that may act as a C3/C6 reprotonation switch for GA. These findings facilitate the rational design or directed evolution of STPSs with structurally diverse skeletons.

Polyvinyl alcohol/carboxymethyl chitosan-based hydrogels loaded with taxifolin liposomes promote diabetic wound healing by inhibiting inflammation and regulating autophagy.

With the improvement of modern living standards, the challenge of diabetic wound healing has significantly impacted the public health system. In this study, our objective was to enhance the bioactivity of taxifolin (TAX) by encapsulating it in liposomes using a thin film dispersion method. Additionally, polyvinyl alcohol/carboxymethyl chitosan-based hydrogels were prepared through repeated freeze-thawing. In vitro and in vivo experiments were conducted to investigate the properties of the hydrogel and its effectiveness in promoting wound healing in diabetic mice. The results of the experiments revealed that the encapsulation efficiency of taxifolin liposomes (TL) was 89.80 ± 4.10 %, with a drug loading capacity of 17.58 ± 2.04 %. Scanning electron microscopy analysis demonstrated that the prepared hydrogels possessed a porous structure, facilitating gas exchange and the absorption of wound exudates. Furthermore, the wound repair experiments in diabetic mice showed that the TL-loaded hydrogels (TL-Gels) could expedite wound healing by suppressing the inflammatory response and promoting the expression of autophagy-related proteins. Overall, this study highlights that TL-Gels effectively reduce wound healing time by modulating the inflammatory response and autophagy-related protein expression, thus offering promising prospects for the treatment of hard-to-heal wounds induced by diabetes.

Hierarchical-unlocking virus-esque NanoCRISPR precisely disrupts autocrine and paracrine pathway of VEGF for tumor inhibition and antiangiogenesis.

Vascular endothelial growth factor (VEGF) not only serves as an autocrine survival factor for tumor cells themselves, but also stimulates angiogenesis by paracrine pathway. Strategies targeting VEGF holds tremendous potential for tumor therapy, however, agents targeting VEGF are limited by intolerable side effects, together with incomplete and temporary blocking of VEGF, resulting in unsatisfactory and unsustained therapeutic outcomes. Herein, hierarchical-unlocking virus-esque NanoCRISPR (HUNGER) is constructed for complete, permanent and efficient intracellular disruption of autocrine and paracrine pathway of VEGF, thereby eliciting notable tumor inhibition and antiangiogenesis. After intravenous administration, HUNGER exhibits prolonged blood circulation and hyaluronic acid-CD44 mediated tumor-targeting capability. Subsequently, when matrix metalloproteinase-2 is overexpressed in the tumor microenvironment, the PEG layer will be removed. The cell-penetrating peptide R8 endows HUNGER deep tumor penetration and specific cellular uptake. Upon cellular internalization, HUNGER undergoes hyaluronidase-triggered deshielding in lysosome, lysosomal escape is realized swiftly, and then the loaded CRISPR/Cas9 plasmid (>8 kb) is transported to nucleus efficiently. Consequentially, complete, permanent and efficient intracellular disruption of autocrine and paracrine pathway of VEGF ensures inhibition of angiogenesis and tumor growth with inappreciable toxicity. Overall, this work opens a brand-new avenue for anti-VEGF therapy and presents a feasible strategy for in vivo delivery of CRISPR/Cas9 system.

Polar Organic Charge-Transfer Complex of the Asymmetrical Component for Flexible Piezoelectric Energy Harvesting and Self-Powered Wearable Sensors.

Organic piezomaterials have attracted much attention because of their easy processing, lightweight, and mechanic flexibility properties. Developing new smart organic piezomaterials is highly required for new-generation electronic applications. Here, we found a novel organic piezomaterial of organic charge-transfer complex (CTC) consisting of dibenzcarbazole analogue (DBCz) and tetracyanoquinodimethane (TCNQ) in the molecular-level heterojunction stacking mode. The DBCz-TCNQ complex exhibited ferroelectric properties (the saturated polarization of ∼1.23 µC/cm2) at room temperature with a low coercive field. The noncentrosymmetric alignment (Pc space group) led to a spontaneous polarization of this architecture and thus was the origin of the piezoelectric behavior. Lateral piezoelectric nanogenerators (PENGs) based on the thermal evaporated CTC thin-film exhibited significant energy conversion behavior under mechanical agitation with a calculated piezoelectric coefficient (d31) of ∼33 pC/N. Furthermore, such a binary CTC thin-film constructed single-electrode PENG could show steady-state sensing performance to external stimuli as this flexible wearable device precisely detected physiological signals (e.g., finger bending, blink movement, carotid artery, etc.) with a self-powered supply. This work provides that the polar CTCs can act as efficient piezomaterials for flexible energy harvesting, conversion, and wearable sensing devices with a self-powered supply, enabling great potential in healthcare, motion detection, human-machine interfaces, etc.