mDia formins form hetero-oligomers and cooperatively maintain murine hematopoiesis.

mDia formin proteins regulate the dynamics and organization of the cytoskeleton through their linear actin nucleation and polymerization activities. We previously showed that mDia1 deficiency leads to aberrant innate immune activation and induces myelodysplasia in a mouse model, and mDia2 regulates enucleation and cytokinesis of erythroblasts and the engraftment of hematopoietic stem and progenitor cells (HSPCs). However, whether and how mDia formins interplay and regulate hematopoiesis under physiological and stress conditions remains unknown. Here, we found that both mDia1 and mDia2 are required for HSPC regeneration under stress, such as serial plating, aging, and reconstitution after myeloid ablation. We showed that mDia1 and mDia2 form hetero-oligomers through the interactions between mDia1 GBD-DID and mDia2 DAD domains. Double knockout of mDia1 and mDia2 in hematopoietic cells synergistically impaired the filamentous actin network and serum response factor-involved transcriptional signaling, which led to declined HSPCs, severe anemia, and significant mortality in neonates and newborn mice. Our data demonstrate the potential roles of mDia hetero-oligomerization and their non-rodent functions in the regulation of HSPCs activity and orchestration of hematopoiesis.

D-allulose 3-epimerase for low-calorie D-allulose synthesis: microbial production, characterization, and applications.

D-allulose, an epimer of D-fructose at C-3 position, is a low-calorie rare sugar with favorable physiochemical properties and special physiological functions, which displays promising perspectives in the food and pharmaceutical industries. Currently, D-allulose is extremely sparse in nature and is predominantly biosynthesized through the isomerization of D-fructose by D-allulose 3-epimerase (DAEase). In recent years, D-allulose 3-epimerase as the key biocatalyst for D-allulose production has received increasing interest. The current review begins by providing a summary of D-allulose regarding its characteristics and applications, as well as different synthesis pathways dominated by biotransformation. Then, the research advances of D-allulose 3-epimerase are systematically reviewed, focusing on heterologous expression and biochemical characterization, crystal structure and molecular modification, and application in D-allulose production. Concerning the constraint of low yield of DAEase for industrial application, this review addresses the various attempts made to promote the production of DAEase in different expression systems. Also, various strategies have been adopted to improve its thermotolerance and catalytic activity, which is mainly based on the structure-function relationship of DAEase. The application of DAEase in D-allulose biosynthesis from D-fructose or low-cost feedstocks through single- or multi-enzymatic cascade reaction has been discussed. Finally, the prospects for related research of D-allulose 3-epimerase are also proposed, facilitating the industrialization of DAEase and more efficient and economical bioproduction of D-allulose.

Transformable self-delivered supramolecular nanomaterials combined with anti-PD-1 antibodies alleviate tumor immunosuppression to treat breast cancer with bone metastasis.

Breast cancer is the most common malignant tumor that threatens women's life and health, and metastasis often occurs in the advanced stage of breast cancer, leading to pathological bone destruction and seriously reducing patient quality of life. In this study, we coupled chlorin e6 (Ce6) with mono-(6-amino-6-deoxy)-beta-cyclodextrin (ß-CD) to form Ce6-CD, and combined ferrocene with the FFVLG3C peptide and PEG chains to form the triblock molecule Fc-pep-PEG. In addition, the IDO-1 inhibitor NLG919 was loaded with Ce6-CD and Fc-pep-PEG to construct the supramolecular nanoparticle NLG919@Ce6-CD/Fc-pep-PEG (NLG919@CF). After laser irradiation, Ce6 produced robust reactive oxidative species to induce tumor cell apoptosis. Simultaneously, ferrocene became charged, and Fc-pep-PEG dissociated from the spherical nanoparticles, enabling their transformation into nanofibers, which increased both the retention effect and the induction of ferroptosis. The released NLG919 reduced the number of regulatory T cells (Tregs) and restored the function of cytotoxic T lymphocytes (CTLs) by inhibiting the activity of IDO-1. Moreover, combined administration with an anti-PD-1 antibody further relieved immune suppression in the tumor microenvironment. This article presents a new strategy for the clinical treatment of breast cancer with bone metastasis and osteolysis.

Design and simulation of an extreme ultraviolet metalens based on the Pancharatnam-Berry phase.

Extreme ultraviolet (EUV) radiation plays a key role in the fields of material science, attosecond metrology, and lithography. However, the reflective optical components typically used in EUV systems contribute to their bulky size, weight, and increased costs for fabrication. In this paper, we theoretically investigate transmissive metalens designs capable of focusing the EUV light based on the Pancharatnam-Berry phase. The designed metalens is composed of nanoscale elliptical holes, which can guide and manipulate EUV light due to the higher refractive index of the vacuum holes compared to that of the surrounding material. We designed an EUV metalens with a diameter of 10 µm, which supports a focal length of 24 µm and a numerical aperture of up to 0.2. It can focus 55-nm EUV incident light to a diffraction-limited spot, and the focusing efficiency is calculated to be as high as about 7% over a broad EUV frequency range (50-65 nm). This study reveals the possibility of applying a dielectric metalens in the EUV region without a transmissive optical material.

Sertraline Is an Effective SARS-CoV-2 Entry Inhibitor Targeting the Spike Protein.

The global spread of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the continuously emerging new variants underscore an urgent need for effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). Here, we screened several FDA-approved amphiphilic drugs and determined that sertraline (SRT) exhibits potent antiviral activity against infection of SARS-CoV-2 pseudovirus (PsV) and authentic virus in vitro. It effectively inhibits SARS-CoV-2 spike (S)-mediated cell-cell fusion. SRT targets the early stage of viral entry. It can bind to the S1 subunit of the S protein, especially the receptor binding domain (RBD), thus blocking S-hACE2 interaction and interfering with the proteolysis process of S protein. SRT is also effective against infection with SARS-CoV-2 PsV variants, including the newly emerging Omicron. The combination of SRT and other antivirals exhibits a strong synergistic effect against infection of SARS-CoV-2 PsV. The antiviral activity of SRT is independent of serotonin transporter expression. Moreover, SRT effectively inhibits infection of SARS-CoV-2 PsV and alleviates the inflammation process and lung pathological alterations in transduced mice in vivo. Therefore, SRT shows promise as a treatment option for COVID-19. IMPORTANCE The study shows SRT is an effective entry inhibitor against infection of SARS-CoV-2, which is currently prevalent globally. SRT targets the S protein of SARS-CoV-2 and is effective against a panel of SARS-CoV-2 variants. It also could be used in combination to prevent SARS-CoV-2 infection. More importantly, with long history of clinical use and proven safety, SRT might be particularly suitable to treat infection of SARS-CoV-2 in the central nervous system and optimized for treatment in older people, pregnant women, and COVID-19 patients with heart complications, which are associated with severity and mortality of COVID-19.

Adsorption and Assembly of Octenyl Succinic Anhydride Starch/Chitosan Electrostatic Complexes at Oil-Water Interface.

Biopolymer electrostatic complexes are popular Pickering stabilizers whose structures greatly affect their interfacial properties. This study comprehensively demonstrated the interfacial adsorption and assembly of dissolved octenyl succinic anhydride (OSA) starch (OSA-D)/chitosan (CS) electrostatic complexes with different structures through complementary characterization methods. We found that compared with single-component systems, OSA-D/CS complexes exhibited significantly increased wetting stability and adsorption rate to the interface, which was reinforced by molecular dynamics simulations. Their soft structures and the entanglement of molecular chains led to the formation of thick and highly viscoelastic multilayer adsorbed films, which greatly resisted deformation against shearing forces. The adsorption and assembly of the complexes were strongly influenced by OSA-D/CS ratios and pH, which could be related to the different interfacial interaction strengths. Overall, the electrostatic complexation, structural characteristics, and interfacial properties of OSA-D/CS complexes were well related, thereby providing valuable information for the regulation of controlled interfaces and bulk system properties.

Formation Mechanism of Starch-Based Double Emulsions from the Interfacial Perspective.

Double emulsions are of significant practical value in protecting the core material owing to their multicomponent structure and have thus been applied in various fields, such as food, cosmetics, and drugs. However, the mechanism of double emulsion formation by native starch is not well established. Herein, we demonstrate a facile route to develop type-A, type-B, and type-C double emulsions using native starch and develop an innovative design for a carrier. Interfacial interaction, enthalpy changes of starch, and interfacial properties are key factors governing the formation of double emulsions and controlling the type of double emulsions formed. Therefore, the results of this study provide a better understanding of how and what type of starch-based double emulsions are formed.

An extensive review: How starch and gluten impact dough machinability and resultant bread qualities.

Wheat flour can form dough with a three-dimensional viscoelastic structure that is responsible for gas holding during fermentation and oven-rise, creating a typical fixed, open-cell foam structure of bread after baking. As the major components of dough, the continuous reticular skeleton formed by gluten proteins and the concentrated starch granules entrapped in gluten matrix predominantly determine dough rheological behaviors and bread qualities. This review surveys the latest literatures and draws out a conclusion from a plethora of information related to the filling effects of starch granules on gluten matrix and the cross-linking mechanisms between gluten proteins and starch granules, which is of great significance to provide sufficient scientific knowledge for development of bread with satisfactory attributes and quality control of end products.

The research advance of resistant starch: structural characteristics, modification method, immunomodulatory function, and its delivery systems application.

Resistant starch, also known as anti-digestion enzymatic starch, which cannot be digested or absorbed in the human small intestine. It can be fermented in the large intestine into short-chain fatty acids (SCFAs) and metabolites, which are advantageous to the human body. Starches can classify as rapidly digestible starch (RDS), slowly digestible starch (SDS), and resistant starch (RS), which possess high thermal stability, low water holding capacity, and emulsification characteristics. Resistant starch has excellent physiological functions such as stabilizing postprandial blood glucose levels, preventing type II diabetes, preventing intestinal inflammation, and regulating gut microbiota phenotype. It is extensively utilized in food processing, delivery system construction, and Pickering emulsion due to its processing properties. The resistant starches, with their higher resistance to enzymatic hydrolysis, support their suitability as a potential drug carrier. Therefore, this review focuses on resistant starch with structural features, modification characteristics, immunomodulatory functions, and delivery system applications. The objective was to provide theoretical guidance for applying of resistant starch to food health related industries.

A review of controlled release from cyclodextrins: release methods, release systems and application.

The controlled release of guest molecules from cyclodextrin (CD) inclusion complexes is very important for specific industrial applications in foods, medicine, cosmetics, textiles, agriculture, environmental protection, and chemical materials. The term "controlled release" encompasses several related methods, including those referred to as immediate release, sustained release and targeted release. Many different CD-based controlled release systems are currently used in practical applications. CD inclusion complexes, CD coupling, supramolecular hydrogels, and supramolecular micelles are among the most common. This review systematically introduces the principles and applications of CD-based controlled release systems, providing a theoretical basis for improving the bioavailability of effective substances and broadening their range of application.

Hypoxia-cleavable and specific targeted nanomedicine delivers epigenetic drugs for enhanced treatment of breast cancer and bone metastasis.

Breast cancer bone metastasis has become a common cancer type that still lacks an effective treatment method. Although epigenetic drugs have demonstrated promise in cancer therapy, their nontargeted accumulation and drug resistance remain nonnegligible limiting factors. Herein, we first found that icaritin had a strong synergistic effect with an epigenetic drug (JQ1) in the suppression of breast cancer, which could help to relieve drug resistance to JQ1. To improve tumor-targeted efficacy, we developed a hypoxia-cleavable, RGD peptide-modified poly(D,L-lactide-co-glycolide) (PLGA) nanoparticle (termed ARNP) for the targeted delivery of JQ1 and icaritin. The decoration of long cleavable PEG chains can shield RGD peptides during blood circulation and reduce cellular uptake at nonspecific sites. ARNP actively targets breast cancer cells via an RGD-αvß3 integrin interaction after PEG chain cleavage by responding to hypoxic tumor microenvironment. In vitro and in vivo assays revealed that ARNP exhibited good biodistribution and effectively suppressed primary tumor and bone metastasis. Meanwhile, ARNP could alleviate bone erosion to a certain extent. Furthermore, ARNP significantly inhibited pulmonary metastasis secondary to bone metastasis. The present study suggests that ARNP has great promise in the treatment of breast cancer and bone metastasis due to its simple and practical potential.

Initial experience with 161 extraperitoneal laparoscopic radical cystectomy procedures: Comparison with transabdominal laparoscopic radical cystectomy.

OBJECTIVES: There is substantial concern about traditional transperitoneal laparoscopic radical cystectomy (TLRC) due to multiple postoperative complications. In contrast, extraperitoneal laparoscopic radical cystectomy (ELRC) appears to cause a lower rate of morbidity. The present study aimed to compare the efficacy of ELRC and TLRC for bladder cancer (BCa). METHODS: The clinical data of patients undergoing laparoscopic radical cystectomy for BCa from April 2018 to October 2021 were retrospectively analyzed, as ELRC and TLRC groups. The postoperative follow-up data of 275 patients were collected and the incidence of postoperative complications and other perioperative outcomes were compared between the two groups. RESULTS: Surgery was successfully completed in all patients without conversion to open surgery. There was no significant difference in the duration of cystectomy surgery (67.32 ± 23.53 vs 72.17 ± 25.72 min, p = 0.106), intraoperative blood loss (178.06 ± 110.4 vs. 174.56 ± 127.40 ml, p = 0.413), or the number of lymph node dissection (15.1 ± 5.7 vs. 14.5 ± 5.1, p = 0.380) between the two groups. The length of stay (11.6 ± 3.8 vs 14.7 ± 5.6 d, p < 0.001), time to resume food intake after surgery (2.3 ± 0.9 vs 3.0 ± 1.3 d, p < 0.001), and the incidence of ileus (p < 0.001) in the ELRC group were significantly lower than in the TLRC group. CONCLUSIONS: ELRC is a safe procedure that can reduce the incidence of postoperative complications, shorten postoperative hospital stay, reduce the duration of recovery of patients, and, therefore, should be promoted.

Designing liquefaction and saccharification processes of highly concentrated starch slurry: Challenges and recent advances.

Starch-based sugars are an important group of starch derivatives used in food, medicine, chemistry, and other fields. The production of starch sugars involves starch liquefaction and saccharification processes. The production cost of starch sugars can be reduced by increasing the initial concentration of starch slurry. However, the usage of the highly concentrated starch slurry is characterized by challenges such as low reaction efficiency and poor product performance during the liquefaction and saccharification processes. In this study, we endeavored to provide a reference guide for improving high-concentration starch sugar production. Thus, we reviewed the effects of substrate concentration on the starch sugar production process and summarized several potential strategies. These regulation strategies, such as physical field pretreatment, complex enzyme-assisted, and temperature control, can significantly increase the starch concentration and mitigate the challenges of using highly concentrated starch slurry. We believe that highly concentrated starch sugar production will achieve a qualitative leap in the future. This review provides theoretical guidance and highlights the importance of high concentration in starch-based sugar production. Further studies are needed to explore the fine structure and enzyme attack mode during the liquefaction and saccharification processes to regulate the production of more targeted products.

Corynoxine suppresses pancreatic cancer growth primarily via ROS-p38 mediated cytostatic effects.

BACKGROUND: Pancreatic cancer is among the most common malignant tumours, and effective therapeutic strategies are still lacking. While Corynoxine (Cory) can induce autophagy in neuronal cells, it remains unclear whether Cory has anti-tumour activities against pancreatic cancer. METHODS: Two pancreatic cancer cell lines, Patu-8988 and Panc-1, were used. Effects of Cory were evaluated by cell viability analysis, EdU staining, TUNEL assay, colony formation assay, and flow cytometry. Quantitative PCR and Western blot were performed to analyse mRNA and protein levels, respectively. In vivo anti-tumour efficacy of Cory was determined by a xenograft model. RESULTS: Cory treatment inhibited cell proliferation, induced endoplasmic reticulum (ER) stress, and triggered apoptosis in the pancreatic cancer cell lines. CHOP knockdown-mediated inhibition of ER stress alleviated the Cory-induced apoptosis but showed a limited effect on cell viability. Cory induced cell death partially via promoting reactive oxygen species (ROS) production and activating p38 signalling. Pretreatment with ROS scavenger N-acetylcysteine and p38 inhibitor SB203580 relieved the Cory-induced inhibition on cell growth. Cory remarkably blocked pancreatic tumour growth in vivo. CONCLUSIONS: Cory exerts an anti-tumour effect on pancreatic cancer primarily via ROS-p38-mediated cytostatic effects. Cory may serve as a promising therapeutic agent for pancreatic cancer.

The modulatory roles and regulatory strategy of starch in the textural and rehydration attributes of dried noodle products.

Noodles are popular staple foods globally, and dried noodle products (DNPs) have gained increasing attention due to recent changes in consumer diet behavior. Rapid rehydration and excellent texture quality are the two major demands consumers make of dried noodle products. Unfortunately, these two qualities conflict with each other: the rapid rehydration of DNPs generally requires a loose structure, which is disadvantageous for good texture qualities. This contradiction limits further development of the noodle industry, and overcoming this limitation remains challenging. Starch is the major component of noodles, and it has two main roles in DNPs. It serves as a skeleton for the noodle in gel networks form or acts as a noodle network filler in granule form. In this review, we comprehensively investigate the different roles of starch in DNPs, and propose strategies for balancing the conflicts between texture and rehydration qualities of DNPs by regulating the gel network and granule structure of starch. Current strategies in regulating the gel network mainly focused on the hydrogen bond strength, the orientation degree, and the porosity; while regulating granule structure was generally performed by adjusting the integrity and the gelatinization degree of starch. This review assists in the production of instant dried noodle products with desired qualities, and provides insights into promising enhancements in the quality of starch-based products by manipulating starch structure.

Periostin deficiency reduces diethylnitrosamine-induced liver cancer in mice by decreasing hepatic stellate cell activation and cancer cell proliferation.

Periostin is a critical extracellular regulator in the pathogenesis of liver disorders such as hepatosteatosis, non-alcoholic steatohepatitis, inflammation, and fibrosis. Periostin is also involved in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms of periostin in hepatic stellate cell (HSC) activation and tumor cell proliferation in the pathogenesis of HCC remain largely unknown. We demonstrate that periostin is markedly upregulated in diethylnitrosamine (DEN)-induced mouse HCC tissues and that periostin knockout impairs DEN-induced HCC development. Periostin is predominantly derived from activated HSCs and periostin deficiency in HSCs impairs HSC activation and inhibits HSC-promoted HCC cell proliferation in vitro and tumor growth in vivo. Mechanistically, periostin promotes HSC activation through the integrin-FAK-STAT3-periostin pathway and augments HCC cell proliferation by activating ERK. There are positive correlations between periostin and HSC activation and cell proliferation in HCC clinical samples. Collectively, our findings demonstrate that HSC-derived periostin promotes HCC development by enhancing HSC activation through an autocrine periostin-integrin-FAK-STAT3-periostin circuit and by augmenting HCC cell proliferation via the ERK pathway in a paracrine manner. Thus, periostin is a multifaceted extracellular regulator in the development of HCC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Suppression Method of Optical Noises in Resonator-Integrated Optic Gyroscopes.

Resonator-integrated optical gyroscopes have advantages such as all-solid-state, on-chip integration, miniaturized structure, and high precision. However, many factors deteriorate the performance and push it far from the shot-noise limited theoretical sensitivity. This paper reviews the mechanisms of various noises and their corresponding suppression methods in resonator-integrated optical gyroscopes, including the backscattering, the back-reflection, the polarization error, the Kerr effect, and the laser frequency noise. Several main noise suppression methods are comprehensively expounded through inductive comparison and reasonable collation. The new noise suppression technology and digital signal processing system are also addressed.

High-Responsivity, Low-Leakage Current, Ultra-Fast Terahertz Detectors Based on a GaN High-Electron-Mobility Transistor with Integrated Bowtie Antennas.

In this study, we fabricated three kinds of terahertz detectors with different leakage currents to analyze the plateau-like effect. The results indicate that the platform becomes increasingly apparent with the decrease in the leakage current. The fabricated device with the lowest leakage current shows a responsivity of 4.9 kV/W and noise equivalent power (NEP) of 72 pW/Hz. Further, it can be used for broadband detection between 215 GHz and 232 GHz with a voltage responsivity of more than 3.4 kV/W, and the response time can be up to 8 ns. Overall, the proposed device exhibits high sensitivity, large modulation frequency, and fast response, which indicates its excellent potential for detection and imaging applications in the THz range, including the detection of the 220 GHz atmospheric window.

Influence of different kinds of fatty acids on the behavior, structure and digestibility of high amylose maize starch-fatty acid complexes.

BACKGROUND: The formation of starch-lipid complexes is of interest to food processing and human nutrition. Fatty acid (FA) structure is important for the formation and structure of starch-FA complexes. However, there is limited research regarding the complexing behavior between amylose and different kinds of FAs, as well as the relationship between fine structures and digestibility of the formed complexes. This study aimed to investigate the behavior, fine structure, and digestibility of complexes formed between high amylose maize starch (HMS) and FA having various chain lengths and unsaturation degrees. RESULTS: Complexes containing different FA structures showed V6III -type crystals. Complexes containing 18-carbon unsaturated FAs displayed significantly higher complexing index (P < 0.05) than other complexes. Complexes containing 12-carbon FAs and 18-carbon FAs with one unsaturation degree showed a higher degree of structural order and resistant starch (RS) content than other complexes. The 12-carbon FAs exhibited a higher binding degree with helical cavity of amylose than other FAs. Additionally, 10-carbon and 18-carbon saturated FAs tended to combine with HMS outside amylose helices more than other FAs. Laser confocal micro-Raman imaging revealed that the physically embedded 10-carbon and 18-carbon saturated FAs showed heterogeneous distribution in complexes, and that the complexed 18-carbon FAs with one unsaturation degree exhibited homogeneous distribution. CONCLUSION: The behavior, structural order and digestibility of complexes could be regulated by FA structure. The 12-carbon FAs and 18-carbon FAs with one unsaturation degree were more suitable for the production of HMS-FA complexes with higher structural order and RS content than other FAs. © 2022 Society of Chemical Industry.

Discovery of 3-aryl substituted benzoxaboroles as broad-spectrum inhibitors of serine- and metallo-ß-lactamases.

The production of ß-lactamases represents the main cause of resistance to clinically important ß-lactam antibiotics. Boron containing compounds have been demonstrated as promising broad-spectrum ß-lactamase inhibitors to combat ß-lactam resistance. Here we report a series of 3-aryl substituted benzoxaborole derivatives, which manifested broad-spectrum inhibition to representative serine-ß-lactamases (SBLs) and metallo-ß-lactamases (MBLs). The most potent inhibitor 9f displayed an IC50 value of 86 nM to KPC-2 SBL and micromolar inhibitory activity towards other tested enzymes. Cell-based assays further revealed that 9f was able to significantly reduce the MICs of meropenem in clinically isolated KPC-2-producing bacterial strains and it showed no apparent toxicity in HEK293T cells.