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Elevated levels of ROS, bacterial infection, inflammation, and improper regeneration are the factors that need to be addressed simultaneously for achieving effective wound healing without scar formation. This study focuses on the fabrication of electrospun ROS-responsive selenium-containing polyurethane nanofibers incorporating deferoxamine mesylate (Def), indomethacin (Indo), and gold nanorods (AuNRs) as proangiogenesis, anti-inflammatory, and antibacterial agents for synchronized delivery to a full-thickness wound in vivo. The structure of the fabricated nanofibers was analyzed by various techniques. Toxicity was checked by CCK-8 and hemolytic assays. The efficiency of wound healing in vitrowas verified by a transwell assay and cell scratch assay. The wound healing efficiency of the nanofibers was assayed in full-thickness wounds in a rat model. The multifunctional nanofibers had a porous structure, enhanced antioxidation, antibacterial activity, and promoted wound healing. They eradicated TNF-α and IL-6, increased IL-10 expression, and revealed the angiogenic potential by increased expression of HIF-1α, VEGF, and CD31.

A combined strategy of calcium-cured alkali roasting and water leaching was devised to treat secondary aluminum dross. The effects of calcium oxide dosage, sodium hydroxide dosage, roasting temperature, and time on aluminum extraction behavior and fluorine curing behavior were studied. Under optimal experimental conditions: roasting temperature of 1000 °C, Al꞉NaOH mole ratio of 1꞉0.6, F꞉CaO mole ratio of 1꞉2.5, and roasting time of 2.0 h, fluorine and aluminum were separated, with 99.98% of the fluoride solidified and 52.97% of the aluminum extracted. The sodium aluminate products obtained by evaporation and crystallization from leaching solution met the industrial standards of China. The aqueous residue can be used as a raw material for quick-setting cement. Overall, this study provides an effective and environmentally friendly strategy for the treatment of secondary aluminum dross.

Ortho-selective C–H borylation of aromatic ketones has not been extensively explored. Herein, we report the iridium-catalyzed ortho-selective C–H borylation of aromatic ketones using in situ-formed imine as the ligand. Good compatibility is observed for various substituted acetophenones and other aromatic ketones, and corresponding products are obtained with medium to excellent yields.

With the increasing use of oral contraceptives and estrogen replacement therapy, the incidence of estrogen-induced cholestasis (EC) has tended to rise. Psoralen (P) and isopsoralen (IP) are the major bioactive components in Psoraleae Fructus, and their estrogen-like activities have already been recognized. Recent studies have also reported that ERK1/2 plays a critical role in EC in mice. This study aimed to investigate whether P and IP induce EC and reveal specific mechanisms. It was found that P and IP increased the expression of esr1, cyp19a1band the levels of E2 and VTG at 80 μM in zebrafish larvae. Exemestane (Exe), an aromatase antagonist, blocked estrogen-like activities of P and IP. At the same time, P and IP induced cholestatic hepatotoxicity in zebrafish larvae with increasing liver fluorescence areas and bile flow inhibition rates. Further mechanistic analysis revealed that P and IP significantly decreased the expression of bile acids (BAs) synthesis genes cyp7a1and cyp8b1, BAs transport genes abcb11band slc10a1,and BAs receptor genes nr1h4and nr0b2a. In addition, P and IP caused EC by increasing the level of phosphorylation of ERK1/2. The ERK1/2 antagonists GDC0994 and Exe both showed significant rescue effects in terms of cholestatic liver injury. In conclusion, we comprehensively studied the specific mechanisms of P- and IP-induced EC and speculated that ERK1/2 may represent an important therapeutic target for EC induced by phytoestrogens.

Propionic acidaemia is a rare disorder caused by defects in the propionyl-coenzyme A carboxylase α or β (PCCA or PCCB) subunits that leads to an accumulation of toxic metabolites and to recurrent, life-threatening metabolic decompensation events. Here we report interim analyses of a first-in-human, phase 1/2, open-label, dose-optimization study and an extension study evaluating the safety and efficacy of mRNA-3927, a dual mRNA therapy encoding PCCA and PCCB. As of 31 May 2023, 16 participants were enrolled across 5 dose cohorts. Twelve of the 16 participants completed the dose-optimization study and enrolled in the extension study. A total of 346 intravenous doses of mRNA-3927 were administered over a total of 15.69 person-years of treatment. No dose-limiting toxicities occurred. Treatment-emergent adverse events were reported in 15 out of the 16 (93.8%) participants. Preliminary analysis suggests an increase in the exposure to mRNA-3927 with dose escalation, and a 70% reduction in the risk of metabolic decompensation events among 8 participants who reported them in the 12-month pretreatment period.

This paper verifies the low Mach number limit of the non-isentropic compressible magnetohydrodynamic (MHD) equations with or without the magnetic diffusion in a three-dimensional bounded domain when the temperature variation is large but finite. The uniform estimates of strong solutions are established in a short time interval independent of the Mach number, provided that the slip boundary condition for the velocity and the Neumann boundary condition for the temperature are imposed and the initial data is well-prepared.

E-portfolios have been adopted by higher education institutions as assessment for learning tools to develop students’ reflective thinking and their ownership of learning. This paper examines how e-portfolios are integrated in an undergraduate course at a Hong Kong university to develop students’ reflective thinking. Based on the qualitative data collected and analysed from both the teacher and students in the course, this paper first discusses the different levels of reflective thinking that the students developed as they were working on their e-portfolios. It then identifies the factors that facilitate and hinder students’ development of reflective thinking, how the facilitating factors are enabled and what the hindering factors need to be addressed. These key findings highlight the pivotal role of the teacher as a learning facilitator and guide, the scaffolding role of the toolkit to support both teachers and students, and the necessity of the technical capacity building and support in the implementation of e-portfolios in higher education.

Formaldehyde-free adhesives are gaining attention due to their compatibility with green production methods. Decorative base paper (DBP) is known for its physical strength and printability and has a high ability for absorbing aldehyde-free adhesives for impregnation. In this paper, DBP was prepared with TiO2and SiO2combined with polyvinyl alcohol (PVA), where the amount of TiO2was reduced in the pulp process. The prepared DBP was impregnated by aldehyde-free adhesive and hot-pressed on wood-based panels. The results showed that upon SiO2coating, the surface smoothness of base paper increased by 132.3 %, whereas the tensile strength increased by 33.6 %. Furthermore, the colour density of cyan, magenta, yellow and black colours increased by 75.4 %, 99.2 %, 51.9 % and 90.5 %, respectively. The surface properties like surface bonding strength and wear resistance of the covered wood-based panels were found to satisfy the standard requirements, which indicates the products can be used for furniture products.

Text detection in complex scene images is a challenging task for intelligent transportation. Existing scene text detection methods often adopt multi-scale feature learning strategies to extract informative feature representations for covering objects of various sizes. However, the sampling operation inherent in multi-scale feature generation can easily impair high-frequency details (e.g., textures and boundaries), which are critical for text detection. In this work, we propose an innovative Hybrid Feature Enhancement Network (dubbed HFENet) to explicitly improve the quality of high-frequency information for detecting texts in scenes and traffic panels. To be concrete, we propose a simple yet effective self-guided feature enhancement module (SFEM) for globally lifting feature representations to highly discriminative and high-frequency abundant ones. Notably, our SFEM is pluggable and will be removed after training without introducing extra computational costs. In addition, due to the challenge and importance of accurately predicting boundaries for text detection, we propose a novel boundary enhancement module (BEM) to explicitly strengthen local feature representations in the guidance of boundary annotation for accurate localization. Extensive experiments on multiple publicly available datasets (i.e., MSRA-TD500, CTW1500, Total-Text, Traffic Guide Panel Dataset, Chinese Road Plate Dataset, and ASAYAR_TXT) verify the state-of-the-art performance of our method.

Objective: Polyphenols are complex compounds containing multiple phenolic hydroxyl groups. They are widely distributed in plants and have antioxidant activities. Whether the antioxidant activities of the cultivated varieties of Echinaceaare similar to or better than those of the wild ones and the relationship between the accumulation of polyphenols and their antioxidant activities are still not clear. Methods: Folin-Ciocalteu method, high performance liquid chromatography (HPLC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, ferric ion reducing antioxidant power (FRAP) assay, 2,2′-azino-bis(3-ethylbenzothiazoline-6)-sulfonic acid (ABTS) radical scavenging assay, and Fe2+chelating ability assay were used, respectively, to detect the total polyphenols and 5 kinds of caffeic acid derivatives (chicoric acid, caffeic acid, caftaric acid, chlorogenic acid, and 1,5-dicaffeoylquinic acid) in the roots, stems, leaves, and flowers, and the antioxidant activities of 3 varieties of Echinacea: E. purpureaL., cultivar E. purpurea‘Aloha’, and E. purpurea‘White Swan’. Results: E. purpureaL. had the highest contents of total polyphenols, 5 caffeic acid derivatives and antioxidant activities, followed by E. purpurea‘White Swan’ and E. purpurea‘Aloha’, respectively. E. purpurea‘White Swan’ had the strongest ability to remove the DPPH, ABTS•+and free radicals, and to chelate Fe2+; E. purpureaL. had the strongest ability to reduce FRAP. The correlation analyses revealed that the contents of total polyphenols and caffeic acid derivatives of E. purpureaL. and E. purpurea‘White Swan’ were correlated with their antioxidant activities. Conclusion: E. purpureaL. was the most appropriate material for the development of medicinal plants. E. purpurea‘White Swan’ could be used as a substitute for E. purpureaL. in terms of its antioxidant activity.

LZTFL1 is a tumor suppressor located in chromosomal region 3p21.3 that is deleted frequently and early in various cancer types including the kidney cancer. However, its role in kidney tumorigenesis remains unknown. Here we hypothesized a tumor suppressive function of LZTFL1 in clear cell renal cell carcinoma (ccRCC) and its mechanism of action based on extensive bioinformatics analysis of patients’ tumor data and validated it using both gain- and loss-functional studies in kidney tumor cell lines and patient-derive xenograft (PDX) model systems. Our studies indicated that LZTFL1 inhibits kidney tumor cell proliferation by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway and inducing cell cycle arrest at G1. Clinically, we found that LZTFL1 is frequently deleted in ccRCC. Downregulation of LZTFL1 is associated with a poor ccRCC outcome and may be used as prognostic maker. Furthermore, we show that overexpression of LZTFL1 in PDX via lentiviral delivery suppressed PDX growth, suggesting that re-expression of LZTFL1 may be a therapeutic strategy against ccRCC.

Propionic acidemia (PA) is an ultrarare disorder caused by deficiency of the mitochondrial enzyme, propionyl-CoA carboxylase (PCC), composed of PCCA and PCCB subunits. An enzyme replacement therapy is being developed using dual messenger RNA (mRNA) therapy composed of lipid nanoparticles (LNPs) encapsulating mRNAs encoding PCCA and PCCB subunits of the PCC enzyme. We herein report on development of a translational semimechanistic pharmacokinetic (PK) and PK/pharmacodynamic (PD) model to quantify the relationship between the mRNA components of mRNA-3927 (an LNP encapsulating PCCA and PCCB mRNAs) and dose levels; PCCA/B mRNA PK and PD responses were assessed as circulating levels of primary disease markers 2-methyl citrate, 3-hydroxypropionate, and propionyl carnitine normalized to acetyl carnitine (C3/C2 ratio) to inform the first-in-human dose range and regimen selection. The translational PK/PD model was developed using preclinical data available in mice with PA, Sprague Dawley rats, and cynomolgus monkeys at dose levels ranging from 0.2 to 9 mg/kg. PCCA/B mRNA PK in mice, rats, and monkeys was adequately described using allometric scaling of volume and clearance parameters. The interspecies preclinical model was scaled allometrically to humans to predict the dose–response relationship in adult and pediatric patients with PA to guide selection of dose range and regimen for the Phase 1 clinical trial (ClinicalTrials.govIdentifier NCT04159103).

Introduction: Postoperative impaired sleep quality and pain are associated with adverse outcomes. Stellate ganglion block (SGB) has shown promising results in enhancing sleep quality and alleviating neuropathic pain. This study aimed to investigate the effects of ultrasound-guided SGB on postoperative sleep quality and pain in patients undergoing breast cancer surgery. Methods: This study is a parallel-group randomized controlled clinical trial with two groups: SGB and control. Fifty female patients undergoing breast cancer surgery were randomized in a 1:1 ratio to receive preoperative ultrasound-guided single-injection SGB (SGB group) or just an ultrasound scan (control group). All participants were blinded to the group assignment. The primary outcome was postoperative sleep quality, assessed by the St. Mary’s Hospital Sleep Questionnaire and actigraphy 2 days postoperatively. The secondary outcome was postoperative pain, measured by the visual analog scale. Results: A total of 48 patients completed the study, with 23 patients in the control group and 25 in the SGB group. The postoperative St. Mary’s Hospital Sleep Questionnaire scores were significantly higher in the SGB group than in the control group on 1 day postoperative (30.88 ± 2.44 versus 27.35 ± 4.12 points, P= 0.001). The SGB also increased the total sleep time and sleep efficiency (main actigraphy indicators) during the first two postoperative nights. Compared with the control group, preoperative SGB reduced postoperative pain and the incidence of breast cancer-related lymphedema (20% versus 52.2%, P= 0.02, odds ratio 0.229, 95% confidence interval 0.064–0.821). There were no adverse events related to SGB. Conclusion: Preoperative ultrasound-guided SGB improves postoperative sleep quality and analgesia in patients undergoing breast cancer surgery. SGB may be a safe and practical treatment to enhance the postoperative quality of life in patients with breast cancer. Trial Registration: The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100046620, principal investigator: Kai Zeng, date of registration: 23 May 2021).

In order to meet the practical application of sodium ion batteries (SIBs), a low energy consumption method is recommended to synthesize the layered NaCrO2cathode materials. Enabled by the larger Na+diffusion coefficients promoted by a proper high temperature, the as-synthesized O3-type NaCrO2material shows superior rate performance even at elevated temperatures, exhibiting 47.4 mA h g−1at 100 C and 60°C. Opposite to the good cyclic capability at room temperature, however, the high-temperature cyclability of NaCrO2deteriorates due to the complex irreversible structural evolution in NaCrO2during cycling at elevated temperatures. This work boosts the industrial development of layered oxide cathode materials for SIBs with outstanding high-rate performance especially at high temperatures, and in the meantime deepens the understanding of the high-temperature capacity decay mechanism for layered oxide cathode materials.

Detecting arbitrary shape scene texts is challenging mainly due to the varied aspect ratios, curves, and scales. In this paper, we propose a novel arbitrary shape scene text detection method via Decoupled Feature Pyramid Networks (DFPN) and regression-based linking (RegLink). Our innovative DFPN decouples the width and height of feature maps generated by FPN to enhance the discriminability of features for varied aspect ratios. As quadrilateral regression results cannot directly represent curve text, we propose a simple yet effective RegLink to link pixels into text instances because pixels in the same curve text have an identical target quadrilateral. Thus, our RegLink can extend the ability of the rotated rectangles text detector for detecting curve text. Besides, we propose a Feature Scale Module to enhance the robustness of features for varied scales. In this way, our method can effectively detect scene texts in arbitrary shapes. Meanwhile, experimental results on three publicly available challenging datasets demonstrate the effectiveness of our method. The code and model of our method is available at https://github.com/lmplayer/DFPN-master.

Background and aims: Ankle brachial index (ABI) is a risk factor for cardiovascular mortality, but it is unclear whether ABI is associated with cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). The current study aimed to evaluate the association between ABI with cardiovascular and all-cause mortality in patients with NAFLD. Methods: We performed a cohort study using the data of the1999–2004 National Health and Nutrition Examination Survey data of adults. Mortality data were followed up to December 2015. NAFLD was defined by the hepatic steatosis index or the US fatty liver index. ABI was classified into three groups: ABI ≤ 0.9 (low value); 0.9 < ABI ≤ 1.1 (borderline value); ABI greater than 1.1 (normal value). Results: We found that low ABI was associated with an increased risk of cardiovascular mortality in patients with NAFLD (HR: 2.42, 95% CI 1.10–5.33 for low value ABI vs normal value ABI, P for trend = 0.04), and the relationship was linearly and negatively correlated in the range of ABI < 1.4. However, low ABI was not associated with all-cause mortality in patients with NAFLD. Stratified by cardiovascular disease, ABI remains inversely correlated with cardiovascular mortality in NAFLD patients without cardiovascular disease. Stratified by diabetes, ABI is inversely correlated with cardiovascular mortality in NAFLD patients regardless of diabetes status. Conclusions: Low ABI is independently associated with higher cardiovascular mortality in NAFLD cases. This correlation remains significant even in the absence of pre-existing cardiovascular disease or diabetes.

Brassicaceae represents an important plant family from both a scientific and economic perspective. However, genomic features related to the early diversification of this family have not been fully characterized, especially upon the uplift of the Tibetan Plateau, which was followed by increasing aridity in the Asian interior, intensifying monsoons in Eastern Asia, and significantly fluctuating daily temperatures. Here, we reveal the genomic architecture that accompanied early Brassicaceae diversification by analyzing two high-quality chromosome-level genomes for Meniocus linifolius(Arabodae; clade D) and Tetracme quadricornis(Hesperodae; clade E), together with genomes representing all major Brassicaceae clades and the basal Aethionemeae. We reconstructed an ancestral core Brassicaceae karyotype (CBK) containing 9 pseudochromosomes with 65 conserved syntenic genomic blocks and identified 9702 conserved genes in Brassicaceae. We detected pervasive conflicting phylogenomic signals accompanied by widespread ancient hybridization events, which correlate well with the early divergence of core Brassicaceae. We identified a successive Brassicaceae-specific expansion of the class I TREHALOSE-6-PHOSPHATE SYNTHASE 1(TPS1) gene family, which encodes enzymes with essential regulatory roles in flowering time and embryo development. The TPS1s were mainly randomly amplified, followed by expression divergence. Our results provide fresh insights into historical genomic features coupled with Brassicaceae evolution and offer a potential model for broad-scale studies of adaptive radiation under an ever-changing environment.

The design and fabrication processes of the stimulated Brillouin laser (SBL) are complex, and it is affected by many factors such as temperature and resonance shift. In this study, we have fabricated a Brillouin laser using a fiber ring resonator with Qfactor = 7.1 × 108and resonance depth (h) = 96%. The free spectral range automatic feedback control technology is proposed to realize the accurate matching of the resonant mode and the Stokes mode. The influence of temperature on the SBL frequency shift is suppressed. The fluctuation range of SBL’s frequency decreases by 5 times. The maximum steady state output of the SBL at the best matching position is realized, and the output power fluctuation range decreases by 15 times. The power stability of the SBL reaches 4.85 × 10−6, which is improved by two orders of magnitude. This simple scheme provides convenience for the application of the SBL, such as sensing and other applications.

Purpose: Visceral adiposity index (VAI) is a reliable indicator for the distribution and function of adipose tissue in the body. The relation of VAI with new-onset type 2 diabetes and new-onset impaired fasting glucose (IFG) remains uncertain. We aimed to investigate the prospective relation of VAI with new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive adults. Methods: A total of 14,838 hypertensive adults free of type 2 diabetes at baseline were included from the China Stroke Primary Prevention Trial. The primary outcome was new-onset type 2 diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary outcome was new-onset IFG, defined as fasting glucose < 6.1 mmol/L at baseline, while fasting glucose ≥ 6.1 mmol/L and < 7.0 mmol/L at the exit visit. Results: Over a median of 4.5 years’ follow-up, 1612 (10.9%) participants developed type 2 diabetes. When VAI was categorized into quartiles, compared with participants in quartile 1–3 (< 2.80), significantly higher risk of new-onset type 2 diabetes (OR 1.30; 95% CI 1.08–1.56) and new-onset IFG (OR 1.28; 95% CI 1.08–1.52) was found in those in quartile 4 (≥ 2.80). Moreover, the positive associations were consistent in participants with or without single abnormal VAI components, including general obesity, abdominal obesity, elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C) levels; or with different numbers of abnormal VAI components (all P interactions > 0.05). Conclusion: Our study suggested a positive relation of VAI with the risk of new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive patients, independent of its components. Level of evidence: Level III, a well-designed cohort.

The microstructure, texture evolution and mechanical properties of AZ31 magnesium alloy were investigated during the cyclic expansion extrusion with the asymmetrical extrusion cavity (CEE-AEC) process. The results show that continuous dynamic recrystallization (CDRX) and discontinuous dynamic recrystallization (DDRX) occur during the CEE-AEC process. After 3 passes, the microstructures of the deformed samples are refined, and the average grain size of the alloys in asymmetrical cavity region is 6.9 μm. The maximum intensities of the basal textures increase with the increase in the number of passes, and the basal textures are deflected during the deformation process. The basal texture of the alloys in asymmetrical cavity region is tilted by approximately ±45° from the normal direction (ND) to the extrusion direction (ED). Grain refinement strengthening and texture deflection significantly improve the comprehensive mechanical properties of the deformed alloys. After 3 passes, tensile yield strength (TYS), ultimate tensile strength (UTS) and elongation-to-failure of the alloy in the asymmetric cavity region are 146 MPa, 230 MPa and 29.7%, respectively.

To date, the robust and durable adhesion capability of hydrogel adhesives in wet environments remains a huge challenge. Herein, a physicochemically double-network crosslinked hydrogel matrix was prepared by mixing acrylic acid (AAc), chitosan (CS) and tannic acid (TA) as the main components and the subsequent in situpolymerization of AAc. The abundant reactive sites on the surface of the hydrogel matrix facilitate rapid, strong and repeatable adhesion to different surfaces of engineering solids and biological tissues in an aquatic environment. The formation of amide covalent bonds resulting from the addition of the bridging agent further expands the long-term application of the hydrogel in tissue repair, and the constructed hydrogel-tissue adhesive interface still has robust adhesion energy after soaking in a physiological environment for up to one month. Moreover, the hydrogel showed fantastic hemostatic performance due to its characteristics of platelet adhesion and high burst pressure. Overall, the persistent adhesion and excellent cytocompatibility of the hydrogel adhesive make it potentially applicable in medical adhesives.

Phagocytosis checkpoints, especially targeting CD47, have shown encouraging therapeutic effects. However, there are currently many shortcomings and challenges with immune checkpoint blockades (ICBs). Inspired by the phenomenon of molecular self-assembly, we modify the CD47 targeting peptide (4N1K) onto the self-assembled peptide FY4, as well as the concatenation of PEG at the other terminal viathe AZO group to construct hypoxia-responsive nanoparticles (PEG-AZO-FY4-4N1K, PAP NPs), utilizing the peptide as a part of the anti-tumor therapy machine. After degradation, PAP NPs can self-assemble to form fibrous networks and anchor CD47 on the surface of tumor cells, promoting their recognition and phagocytosis by macrophages and relieving immune escape. Self-assembled peptides can interweave on the surface of tumor cells, fully exploiting their morphological advantages to impede normal cell interaction and metastasis. The PAP NPs work synergistically with Doxorubicin (DOX) to further maximize the efficacy of chemoimmunotherapy. In conclusion, this strategy pioneers the progress of self-assembled peptides in biomedicine and promises a novel breakthrough in the development of checkpoint inhibitor therapies.

Long noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown. VHLdeficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy.

Hydrogel adhesives with integrated functionalities are still required to match their ever‐expanding practical applications in the field of tissue repair and regeneration. A simple and effective safety strategy is reported, involving an in situ injectable polymer precursor and visible light‐induced cross‐linking. This strategy enables the preparation of a hydrogel adhesive in a physiological environment, offering wet adhesion to tissue surfaces, molecular flexibility, biodegradability, biocompatibility, efficient hemostatic performance, and the ability to facilitate liver injury repair. The proposed one‐step preparation process of this polymer precursor involves the mixing of gelatin methacryloyl (GelMA), poly(thioctic acid) [P(TA)], poly(acrylic acid)/amorphous calcium phosphate (PAAc/ACP, PA) and FDA‐approved photoinitiator solution, and a subsequent visible light irradiation after in situ injection into target tissues that resulted in a chemically‐physically cross‐linked hybrid hydrogel adhesive. Such a combined strategy shows promise for medical scenarios, such as uncontrollable post‐traumatic bleeding. An injectable precursor solution containing a light initiator forms an adhesive hydrogel on tissues. Notably, the hydrogel possesses both biocompatibility and biodegradability, enabling safe and efficient prevention of tissue bleeding while promoting the repair of liver injuries.

Introduction: The coronavirus disease 2019 (COVID-19) was defined as a species of beta coronavirus causing atypical respiratory disease in humans. The COVID-19 pandemic has resulted in an unprecedented health and economic crisis worldwide. Little is known about the specifics of its influence on people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA). In this study, we aim to investigate the prevalence and mortality in PLWHA co-infected with COVID-19. Methods: The databases PUBMED, EMBASE, BioRxiv, and medRxiv were searched up to 9 March 2021 to explore the prevalence and mortality rate of COVID-19 in PLWHA. Cohort studies and case series meeting the inclusion criteria were included in this review. Results: We identified 14 eligible studies, 9 of which were cohort and 5 were case series. A total of 203,761 patients with COVID-19 were identified (7718 PLWHA vs. 196,043 non-PLWHA). Meta-analyses estimated the prevalence and mortality rate of COVID-19 in PLWHA was 0.774% [95% confidence interval (CI) 0.00393–0.01517] and 8.814% (95% CI 0.05766–0.13245) respectively. COVID-19 co-infected PLWHA do not seem to be associated with higher mortality, as compared to non-PLWHA [relative risk (RR) 0.96 (95% CI 0.88–1.06)]. The presence of comorbidities such as diabetes mellitus, RR 5.2 (95% CI 4.25–6.36), hypertension and chronic cardiac disease, RR 4.2 (95% CI 1.09–16.10), and chronic kidney disease, RR 8.43 (95% CI 5.49–12.93) were associated with an increased mortality in COVID-19 co-infected PLWHA. Conclusion: The estimated prevalence and mortality rate of COVID-19 in PLWHA were 0.774% and 8.814%, respectively. Since most of the included studies used unmatched populations, comparisons between PLWHA and non-PLWHA should be interpreted with caution. Further investigations are needed for a more comprehensive understanding of the relationship between cluster of differentiation 4 cell count, HIV viral load, antiretroviral therapy, and COVID-19 related prognosis in PLWHA.

ABSTRACTResveratrol (Res) has been shown to exhibit anti-cancer properties in gastric cancer. However, its clinical application is limited by its poor pharmacokinetics, stability, and low solubility. Hence, this study aimed to explore and verify a better delivery system for gastric cancer therapy. Using transmission electron microscopy, Fourier transform infrared (FTIR) spectroscopy, and ultraviolet (UV) spectrometry, we observed the shape and encapsulation of resveratrol-modified mesoporous silica nanoparticles (MSN-Res) that were synthesized by chemical methods. To explore the anti-cancer effects of these MSN-Res in vivo and in vitro, we established AGS and HGC-27 tumor-bearing mouse models. Meanwhile, the proliferation of gastric cancer cells in vitro and in vivo was assessed by Cell Counting Kit-8, EdU, and Ki-67 immunohistochemical staining methods, while cellular apoptosis, and invasion and migration were detected by TdT-mediated dUTP nick end labeling (TUNEL) and Transwell assays, respectively. FTIR and UV results showed that we successfully synthesized and loaded drugs. Safety evaluation experiments showed that neither MSN-SH nor MSN-Res had toxic effects on the normal tissues of animals. Moreover, in vitro experiments revealed that MSN-Res significantly inhibited the proliferation, invasion, and migration of gastric cancer cells. Furthermore, TUNEL assay showed that MSN-Res promoted apoptosis in gastric cancer. These results were confirmed by the nude mouse tumorigenesis experiment. In conclusion, we demonstrated that MSN-Res showed better inhibitory effect on the development of gastric cancer than Res alone, indicating that MSN-Res could be a promising drug delivery system for gastric cancer treatment.

The cycloaddition mechanisms of CO2and epichlorohydrin catalyzed by salophen as an organocatalyst were investigated using B3LYP density functional theory computations. The kinetically most favored neutral pathway involves a concerted and synergistic mechanism of phenolate as a nucleophile and phenol as a H-bonding donor in epoxide ring opening and CO2addition. The computed apparent barrier (33 kcal mol−1) is in line with the reaction conditions (120 °C and 10 bar CO2). A similar and anionic route with a much lower apparent barrier (17 kcal mol−1) to react under milder conditions has been proposed and this has to be proven experimentally.

Hyperglycemic micro‐environment induced by diabetes could regulate the response of periodontal tissues to pathogenic microorganisms in which disruption of autophagy lysosomal pathway (ALP) may participate. This study aimed to explore the mechanisms underlying how high glucose (HG) regulates ALP in gingival epithelial cells (GECs). Human gingival tissues in healthy group (C), periodontitis group (P), diabetes group (DM), and diabetes + periodontitis group (DP) were collected and were applied to observe the fusion of autophagy and lysosome. Diabetic mouse model with periodontitis was established and RNA‐seq was applied to investigate the expression of ALP‐associated genes in gingival epithelium. To explore the key role of ATPase transmembrane v0 domain, subunit c (ATP6V0C) in the disruption of ALP by HG, human gingival epithelial cells (HGECs) were cultured in 5.5 mM/25 mM glucose medium for 48 hours and followed by Porphyromonas gingivalisstimulation for 0, 6, and 12 hours. HBLV‐h‐ATP6V0Cwas transfected in HGECs that were stimulated by 25 mM HG condition. Immunofluorescence double staining exhibited the disruption of ALP in human gingival epithelium in diabetes groups and HGECs under 25 mM glucose condition, accompanied with significantly downregulated lysosomal acidity. RNA‐seq of mouse gingival epithelium screened out Atp6v0c. Compared with HGECs in normal culture medium, ATP6V0C expression and LC3‐II/I expression ratio were significantly downregulated, with an upregulated expression of P62, IL‐1β in HGECs under HG condition. Over‐expression of ATP6V0C rescued HG‐induced disruption of ALP in HBLV‐h‐ATP6V0Ctransfected HGECs, with significantly upregulation of LC3‐II/I and downregulation of P62, IL‐1β. ATP6V0C mediates HG‐induced ALP disruption in HGECs, eventually exacerbates periodontal inflammation.

Communicated by Ramaswamy H. Sarma

ABSTRACTThe kinetics and mechanism of the reduction of manganese dioxide ore by calcium lignosulfonate (CLS) in acid solution were investigated. The results showed that the reducing process mainly occurred after the adsorption and then decomposition of CLS by ore and the concentration of sulphuric acid exerted an enhancing effect on both CLS adsorption and manganese extraction. The effects of leaching temperature, the mass ratio of CLS to MnO2in ore, concentration of sulphuric acid as well as leaching time on per cent leached of Mn were also discussed. The experimental data were well interpreted with a shrinking core model of internal diffusion, and an overall kinetic model was established. The reaction rate constant was found to be proportional to the mass ratio of CLS to MnO2in ore and concentration of sulphuric acid, and the apparent activation energy was determined to be 69.4 kJ mol−1by using Arrhenius expression.

Background: Anthocyanins are a type of flavonoids that are natural water soluble glycosidic pigments with efficacious anti-cancer effects, which have good biological activity against many cancers including colorectal cancer (CRC). However, the exact molecular mechanism used by anthocyanins against cancer is unclear; it is also unclear what a reasonable dosage might be for their use against colorectal cancer. Methods: Western blotting, immunohistochemistry, MTT assay, xenograft model, and hematoxylin-eosin (HE) staining were used to perform the experiments. Results: Compared with the control group, anthocyanins could significantly inhibit the cell viability and proliferation and promote the apoptosis of human colon cancer HT29 cells. Furthermore, anthocyanins reduced tumor weight and volume in a colon tumor mouse model and downregulated the expression of PI3K protein, inhibited AKT expression and phosphorylation, decreased the Bcl-2 and Bax ratio and reduced survivin protein expression in the tumor tissue. Conclusion: Anthocyanins promoted apoptosis of CRC cells and inhibited colon cancer growth of xenografted tumors. Mechanistically, anthocyanins enhanced the Bcl-2/Bax and caspase-dependent apoptotic pathways through targeting the PI3K/AKT/survivin pathway, resulting in impairment of growth of CRC.

The thermal oxidation characteristics of abietic acid were investigated through tracing the oxidation process in custom-designed mini closed pressure vessel test under isothermal and step temperature conditions. Peroxide generation and the peroxide value of abietic acid oxidation process were measured using thin-layer chromatographic analysis and iodimetry. The primary oxidation product—peroxide—was separated by column chromatography with further structure characterization, and its thermal decomposition characteristics were assessed via a differential scanning calorimeter (DSC). The oxidation was mainly initiated through the radical generation from hydrogen abstraction on the unsaturated conjugated double bonds of abietic acid above 343 K. The main hydroperoxide, 7-hydroperoxy-13-abiet-8(14)-enoic acid, was found in abietic acid with a high peroxide value. The exothermic onset temperature (T0) and decomposition heat (QDSC) of this peroxide were 353.94 K and 545.37 J·g–1, respectively. Finally, a second-stage oxidation process of abietic acid was first investigated when the temperature reached the abietic acid melt point (448 K) with complex oxidation products forming, such as dehydroabietic acid, palustric acid, 7-oxodehydroabietic acid, neoabietic acid, 7-methoxy-tetradehydroabietic acid, 12-deoxyroyleanone acid, and 12-methoxy-abietic acid.

The title marine natural products have been prepared by total synthesis and in the case of congeners 3, 6, and 7for the first time. Each of these was obtained by manipulation of readily prepared denigrin B (2). The structure, 3, assigned to denigrin C is shown to be incorrect. Reaction of compound 2with DDQ has led, in high yield, to the related natural product spirodactylone (16), while treating the corresponding permethyl ether 15with PIFA/BF3·Et2O provides compound 20, embodying an isomeric framework.

This work reports the mild and efficient Ru-catalyzed trifluoroisopropylation of arenes using 2-bromo-1,1,1-trifluoropropane. Various bioactive molecules, such as purine and nucleoside derivatives, were well-suited for this transformation, affording the corresponding products in moderate-to-good yields. This method provides an efficient strategy for synthesizing trifluoroisopropyl molecules for drug discovery.

The dynamic Stokes shift of coumarin 153, measured with a combination of broad-band fluorescence upconversion (80 fs resolution) and time-correlated single photon counting (to 20 ns), is used to determine the complete solvation response of 21 imidazolium, pyrrolidinium, and assorted other ionic liquids. The response functions so obtained show a clearly bimodal character consisting of a subpicosecond component, which accounts for 10–40% of the response, and a much slower component relaxing over a broad range of times. The times associated with the fast component correlate with ion mass, confirming its origins in inertial solvent motions. Consistent with many previous studies, the slower component is correlated to solvent viscosity, indicating that its origins lie in diffusive, structural reorganization of the solvent. Comparisons of observed response functions to the predictions of a simple dielectric continuum model show that, as in dipolar solvents, solvation and dielectric relaxation involve closely related molecular dynamics. However, in contrast to dipolar solvents, dielectric continuum predictions systematically underestimate solvation times by factors of at least 2–4.

The rates of excited-state intramolecular electron transfer in 9-(4-biphenyl)-10-methylacridinium (BPAc+), crystal violet lactone (CVL), and bianthryl have been measured in a variety of ionic liquids using time-correlated single-photon counting. All three of these reactions had previously been studied in conventional dipolar solvents and their reaction rates shown to be controlled by solvation dynamics. The main focus of this work is to ask whether the same relationships between reaction and solvation times already established in dipolar solvents also apply in ionic liquids. In BPAc+, where reaction conforms to a simple two-state kinetic scheme and reaction rates are easily measured, the result is a clear “yes”. In the case of bianthryl, whose spectra reflect the more complex kinetics of a barrierless process, the answer is also yes. In contrast to other recent studies of bianthryl, the present results demonstrate that the same equality between (integral) reaction times and solvation times observed in conventional solvents also applies in ionic liquids. Finally, the case of CVL is less clear due to the greater uncertainty associated with the data afforded by this weak fluorophore, combined with a lack of data in conventional solvents having large solvation times. But the CVL reaction can also be reasonably interpreted as exhibiting a common behavior in dipolar and ionic solvents.

When mining near the fault can cause the fault to slip and release energy, resulting in rockburst and posing a significant safety risk to coal mine production. This paper proposes a numerical simulation method, based on FLAC3D numerical simulation, for calculating the dynamic response of fault slip below the impact of mining. The release patterns of energy from fault slip are compared between mining via the fault from the hanging wall and mining via the fault from the footwall. The dynamic response characteristics of coal and rock mass under the disturbance of fault slip induced dynamic loading are revealed. This research suggests that the fault slip seismic moment (M0) of the panel mined via the fault from footwall is substantially higher than from hanging wall. Moreover, the disturbance of the footwall panel mining via the fault leads to a more severe disturbance of the surrounding rock mass, resulting in a higher risk of rockburst. Plastic failure of the rock surrounded in the mining area under the strong dynamic loading of fault slip leads to a significant reduction in peak abutment stress, releasing tremendous energy. When the disturbance caused by fault slip dynamic load is relatively small, the maximum abutment stress increases, and the dynamic load increases the energy storage of surrounding rock. Based on energy theory, an energy criterion for the occurrence of fault slip type rockburst has been proposed. The results suggest that strong fault slip dynamic load has an obvious inducing effect on rockburst, and the stronger the dynamic load and greater static load of the rock, the more the manifestation of rockburst.

Making use of temperature-controlled thiation as a key operation, a simple route to 2-aminothiophenes or thieno[2,3-c]isothiazoles has been newly developed wherein the 2-aminothiophene nucleus was formed through an initial formation of thioamide followed by a 5-exo-dig addition to the tethered alkyne; however, under harsher thermal conditions, excess sulfur-transferring reagents enabled further oxidative thiation to generate the corresponding thieno[2,3-c]isothiazoles.

Lactose fatty acid esters are high-value-added derivatives of lactose and represent a class of biodegradable, non-ionic, low-molecular-weight surfactants (emulsifiers) that have considerable potential in the food, cosmetic, and pharmaceutical industries. Certain lactose esters have also garnered attention for their biological activities. In this work, we detail syntheses of a homologous series of 6′-O-acyllactose esters of varying alkyl chain length (from 6 to 18 carbons) and report on their activities as surfactants as well as their antimicrobial and cytotoxic properties. The structure–property profiles established in this work revealed that while the medium-chain esters displayed excellent emulsifying properties and moderate antimicrobial activities, their longer chain congeners exhibited the highest cytotoxicities. As such, we have established that certain 6′-O-acyllactose esters are superior to their sucrose-derived and commercially exploited counterparts. These results will serve as a useful guide for the development of lactose esters as, inter alia, emulsifiers in the food industry.

Detection of asymptomatic or subclinical novel human coronavirus SARS-CoV-2 infection is critical for understanding the overall prevalence and infection potential of COVID-19. To estimate the cumulative prevalence of SARS-CoV-2 infection in China, we evaluated the host serologic response, measured by the levels of immunoglobulins M and G in 17,368 individuals, in the city of Wuhan, the epicenter of the COVID-19 pandemic in China, and geographic regions in the country, during the period from 9 March 2020 to 10 April 2020. In our cohorts, the seropositivity in Wuhan varied between 3.2% and 3.8% in different subcohorts. Seroposivity progressively decreased in other cities as the distance to the epicenter increased. Patients who visited a hospital for maintenance hemodialysis and healthcare workers also had a higher seroprevalence of 3.3% (51 of 1,542, 2.5–4.3%, 95% confidence interval (CI)) and 1.8% (81 of 4,384, 1.5–2.3%, 95% CI), respectively. More studies are needed to determine whether these results are generalizable to other populations and geographic locations, as well as to determine at what rate seroprevalence is increasing with the progress of the COVID-19 pandemic. Serologic surveillance has the potential to provide a more faithful cumulative viral attack rate for the first season of this novel SARS-CoV-2 infection.

The oncolytic viruses now hold a promise of new therapeutic strategy for cancer. Its concept has inspired a wave of commercial research and development activities for the products of this category in China since 1998. The first commercialized oncolytic virus product in the world, Oncorine (H101), developed by Shanghai Sunway Biotech Co., Ltd since 1999, was approved by Chinese SFDA in November, 2005 for nasopharyngeal carcinoma in combination with chemotherapy after the phase III clinical trial, and finally acquired GMP certificate in August, 2006. This review introduces how Oncorine was successfully developed in China, and how the Chinese market responded after it was launched into the market in 2006.