Dicoumarol attenuates NLRP3 inflammasome activation to inhibit inflammation and fibrosis in knee osteoarthritis.

Knee osteoarthritis (KOA) is a major cause of disability in elderly individuals. Dicoumarol is a coumarin­like compound derived from sweet clover [Melilotus officinalis (L.) Pall]. It has been suggested that dicoumarol exhibits various types of pharmacological activities, including anticoagulant, antitumor and antibacterial effects. Due to its various biological activities, dicoumarol has a potential protective effect against OA. Therefore, the present study aimed to assess the effects of dicoumarol on knee osteoarthritis. In the present study, dicoumarol was found to protect rat synoviocytes from lipopolysaccharide (LPS)­induced cell apoptosis. Western blot analysis showed that dicoumarol significantly reduced the protein expression levels of fibrosis­related markers and inflammatory cytokines (Tgfb, Timp, Col1a, Il1b and Il18). The inhibitory rates of these proteins were all >50% (P<0.01) compared with those in the LPS and ATP­induced group. Consistently, the mRNA expression levels of these markers and cytokines were decreased to normal levels by dicoumarol after the treatment of rat synovial fibroblasts with LPS and ATP. Mechanistic studies demonstrated that dicoumarol did not affect NF­κB signaling, but it did directly interact with NOD­like receptor protein 3 (NLRP3) to promote its protein degradation, which could be reversed by MG132, but not NH4Cl. The protein half­life of NLRP3 was accelerated from 26.1 to 4.3 h by dicoumarol. Subsequently, dicoumarol could alleviate KOA in vivo; knee joint diameter was decreased from 11.03 to 9.93 mm. Furthermore, the inflammation and fibrosis of the knee joints were inhibited in rats. In conclusion, the present findings demonstrated that dicoumarol could impede the progression of KOA by inhibiting NLRP3 activation, providing a potential treatment strategy for KOA.

Construction of MXene-mediated inorganic-organic quaternary ammonium salt-hybrid coating for fire safety and multi-mode synergistic antibacterial of cotton fabric.

With the continuous development of the society, there is a growing demand for the durability, versatility and multifunction of cott fabrics. In this work, the cotton fabric is coated with multifunctional coating via dip-coating of transition metal carbide (MXene) and then encapsulation of dimethyloctadecyl [3-trimethoxysilopropyl] ammonium chloride (QAS). In view of MXene with excellent light absorption and photothermal conversion efficiency, the controllable antibacterial performance of the cotton fabric is further improved. Benefiting from the encapsulation of QAS, CF@P@M@QAS fabric shows mechanical stability (24 h washing, 1000 cycles folding test and 100 cyclic abrasion) and hydrophobicity. Meantime, the QAS on the surface of multifunctional cotton fabric significantly increases antibacterial activity, and the antibacterial rate can reach to 100 % against Staphylococcus aureus (S. aureus) and 98 % Escherichia coli (E. coli). Besides, CF@P@M@QAS cotton fabric also integrates functions of fire safety and physical therapy. Thus, this multifunctional cotton fabric based MXene offers a novel solution for extending its application in medical electronics and physical therapy.

Boosting Cathode Activity and Anode Stability of Lithium-Sulfur Batteries with Vigorous Iodic Species Triggered by Nitrate.

Lithium-sulfur (Li-S) battery with a sulfurized polyacrylonitrile cathode is a promising alternative to Li-ion systems. However, the sluggish charge transfer of cathode and accumulation of inactive Li on anode remain persistent challenges. An advanced electrolyte additive with function towards both cathode and anode holds great promise to address these issues. Herein, we present a new strategy to boost sulfur activity and rejuvenate dead Li simultaneously. In the polar electrolyte containing I2-LiNO3 additives, I3 -/IO3 - are triggered significantly by the reaction between NO3 - and I- ions. The I3 -/IO3 - are reactive to insulated Li2S product of cathode and inactive Li on anode, thus accelerating the conversion reaction of sulfur and recovering Li sources back to battery cycling. The in situ/ex situ spectroscopic and morphologic monitoring reveal the crucial role of iodine in promoting Li2S dissociation and inhibiting dendritic Li growth. With the modified electrolyte, the symmetric Li||Li cells deliver a lifespan of 4000 h with an overpotential less than 12 mV at 0.5 mA cm-2. For Li-S cells, 100 % capacity retention up to thousands of cycles and enhanced rate capability are available. This work demonstrates a feasible strategy on electrolyte engineering for practical applications of Li-S batteries.

Metal-organic-framework derived NiS2/C hollow structures for enhanced polysulfide redox kinetics in lithium-sulfur batteries.

To cope with the shuttling of soluble lithium polysulfides in lithium-sulfur batteries, confinement tactics, such as trapping of sulfur within porous carbon structures, have been extensively studied. Although performance has improved a bit, the slow polysulfide conversion inducing fast capacity decay remains a big challenge. Herein, a NiS2/carbon (NiS2/C) composite with NiS2 nanoparticles embedded in a thin layer of carbon over the surface of micro-sized hollow structures has been prepared from Ni-metal-organic frameworks. These unique structures can physically entrap sulfur species and also influence their redox conversion kinetics. By improving the reaction kinetics of polysulfides, the NiS2/carbon@sulfur (NiS2/C@S) composite cathode with a suppressed shuttle effect shows a high columbic efficiency and decent rate performance. An initial capacity of 900 mAh g-1 at the rate of 1 C (1 C = 1675 mA g-1) and a low-capacity decline rate of 0.132% per cycle after 500 cycles are obtained, suggesting that this work provides a rational design of a sulfur cathode.

Highly Sensitive Gas Sensor for Detection of Air Decomposition Pollutant (CO, NOx): Popular Metal Oxide (ZnO, TiO2)-Doped MoS2 Surface.

When partial discharges occur in air-insulated equipment, the air decomposes to produce a variety of contamination products, resulting in a reduction in the insulation performance of the insulated equipment. By monitoring the concentration of typical decomposition products (CO, NO, and NO2) within the insulated equipment, potential insulation faults can be diagnosed. MoS2 has shown promising applications as a gas-sensitive semiconductor material, and doping metal oxides can improve the gas-sensitive properties of the material. Therefore, in this work, MoS2 has been doped using the popular metal oxides (ZnO, TiO2) of the day, and its gas-sensitive properties to the typical decomposition products of air have been analyzed and compared using density functional theory (DFT) calculations. The stability of the doped system was investigated using molecular dynamics methods. The related adsorption mechanism was analyzed by adsorption configuration, energy band structure, density of states (DOS) analysis, total electron density (TED) analysis, and differential charge density (DCD) analysis. Finally, the practical application of related sensing performance is evaluated. The results show that the doping of metal oxide nanoparticles greatly improves the conductivity, gas sensitivity, and adsorption selectivity of MoS2 monolayer to air decomposition products. The sensing response of ZnO-MoS2 for CO at room temperature (25 °C) reaches 161.86 with a good recovery time (0.046 s). TiO2-MoS2 sensing response to NO2 reaches 3.5 × 106 at 25 °C with a good recovery time (0.108 s). This study theoretically solves the industrial challenge of recycling sensing materials and provides theoretical value for the application of resistive chemical sensors in air-insulated equipment.

A self-stabilized and water-responsive deliverable coenzyme-based polymer binary elastomer adhesive patch for treating oral ulcer.

Oral ulcer can be treated with diverse biomaterials loading drugs or cytokines. However, most patients do not benefit from these materials because of poor adhesion, short-time retention in oral cavity and low drug therapeutic efficacy. Here we report a self-stabilized and water-responsive deliverable coenzyme salt polymer poly(sodium α-lipoate) (PolyLA-Na)/coenzyme polymer poly(α-lipoic acid) (PolyLA) binary synergistic elastomer adhesive patch, where hydrogen bonding cross-links between PolyLA and PolyLA-Na prevents PolyLA depolymerization and slow down the dissociation of PolyLA-Na, thus allowing water-responsive sustainable delivery of bioactive LA-based small molecules and durable adhesion to oral mucosal wound due to the adhesive action of PolyLA. In the model of mice and mini-pig oral ulcer, the adhesive patch accelerates the healing of the ulcer by regulating the damaged tissue inflammatory environment, maintaining the stability of oral microbiota, and promoting faster re-epithelialization and angiogenesis. This binary synergistic patch provided a therapeutic strategy to treat oral ulcer.

A Stabilized Li-Metal Anode with a Ti-Based Metal-Organic Framework Electronic Shield.

The insufficient cyclic efficiency and poor safety have prohibited the commercial applications of the lithium-metal anode because of its uncontrolled dendrite growth at the surface. A mechanically stable and highly ionic conductive solid electrolyte interphase (SEI) holds great promise to address the issues. Herein, a viable surface engineering approach is proposed for stabilizing the Li anode via a scalable artificial method. The surface of Li metal is functionalized by constructing a mechanically tough and electron-insulating metal-organic framework (MOF) of the MIL-125(Ti) layer. In-situ optical microscopy reveals its crucial role in inhibiting dendritic Li growth. Because of the intrinsic insulativity and highly ordered micropores of MIL-125(Ti), the Li+ ions acquire electrons under the coating layer, resulting in a uniform and dense Li deposition behavior. The symmetric cell of the MOF-modified Li electrode delivers a long life span of 2000 h with an overpotential of less than 20 mV at 0.5 mA cm-2. When paired with the same MOF-derived sulfur cathode, decent cycling retention is available as well. This work demonstrates a feasible strategy for the development of a stable Li-metal anode with alleviative dendritic growth.

Central-cell-produced attractants control fertilization recovery.

Animal fertilization relies on hundreds of sperm racing toward the egg, whereas, in angiosperms, only two sperm cells are delivered by a pollen tube to the female gametes (egg cell and central cell) for double fertilization. However, unsuccessful fertilization under this one-pollen-tube design can be detrimental to seed production and plant survival. To mitigate this risk, unfertilized-gamete-controlled extra pollen tube entry has been evolved to bring more sperm cells and salvage fertilization. Despite its importance, the underlying molecular mechanism of this phenomenon remains unclear. In this study, we report that, in Arabidopsis, the central cell secretes peptides SALVAGER1 and SALVAGER2 in a directional manner to attract pollen tubes when the synergid-dependent attraction fails or is terminated by pollen tubes carrying infertile sperm cells. Moreover, loss of SALs impairs the fertilization recovery capacity of the ovules. Therefore, this research uncovers a female gamete-attraction system that salvages seed production for reproductive assurance.

Synthesis of Oxo-Bridged Dibenzoazocines through Ruthenium-Catalyzed [4 + 3]-Cycloannulation of Aza-ortho-quinone Methides with Carbonyl Ylides.

Oxo-bridged dibenzoazocines are furnished within a single synthetic step at room temperature via ruthenium-catalyzed [4 + 3]-cycloannulation of aza-ortho-quinone methides with carbonyl ylides. Exclusive diastereoselectivity, excellent yield, mild reaction conditions, and broad substrate scope are distinguishing features of this protocol. The product could be prepared on a gram scale and could be further functionalized into diverse substituted dihydroisobenzofuran derivatives and a dibenzoazocine scaffold.

Homeostasis of flavonoids and triterpenoids most likely modulates starch metabolism for pollen tube penetration in rice.

In angiosperms, the timely delivery of sperm cell nuclei by pollen tube (PT) to the ovule is vital for double fertilization. Penetration of PT into maternal stigma tissue is a critical step for sperm cell nuclei delivery, yet little is known about the process. Here, a male-specific and sporophytic mutant xt6, where PTs are able to germinate but unable to penetrate the stigma tissue, is reported in Oryza sativa. Through genetic study, the causative gene was identified as Chalcone synthase (OsCHS1), encoding the first enzyme in flavonoid biosynthesis. Indeed, flavonols were undetected in mutant pollen grains and PTs, indicating that the mutation abolished flavonoid biosynthesis. Nevertheless, the phenotype cannot be rescued by exogenous application of quercetin and kaempferol as reported in maize and petunia, suggesting a different mechanism exists in rice. Further analysis showed that loss of OsCHS1 function disrupted the homeostasis of flavonoid and triterpenoid metabolism and led to the accumulation of triterpenoid, which inhibits significantly α-amylase activity, amyloplast hydrolysis and monosaccharide content in xt6, these ultimately impaired tricarboxylic acid (TCA) cycle, reduced ATP content and lowered the turgor pressure as well. Our findings reveal a new mechanism that OsCHS1 modulates starch hydrolysis and glycometabolism through modulating the metabolic homeostasis of flavonoids and triterpenoids which affects α-amylase activity to maintain PT penetration in rice, which contributes to a better understanding of the function of CHS1 in crop fertility and breeding.

iASMP: An interpretable in-silico predictive tool focusing on species-specific antimicrobial peptides.

Antimicrobial peptides (AMPs), a crucial part of the innate immune system, have been exploited as promising candidates for antibacterial agents. Many researchers have been devoting their efforts to develop novel AMPs in recent decades. In this term, many computational approaches have been developed to identify potential AMPs accurately. However, finding peptides specific to a particular bacterial species is challenging. Streptococcus mutans is a pathogen with an apparent cariogenic effect, and it is of great significance to study AMP that inhibit S. mutans for the prevention and treatment of caries. In this study, we proposed a sequence-based machine learning model, namely iASMP, to exactly identify potential anti-S. mutans peptides (ASMPs). After collecting ASMPs, the performances of models were compared by utilizing multiple feature descriptors and different classification algorithms. Among the baseline predictors, the model integrating the extra trees (ET) algorithm and the hybrid features exhibited optimal results. The feature selection method was utilized to remove redundant feature information to improve the model performance further. Finally, the proposed model achieved the maximum accuracy (ACC) of 0.962 on the training dataset and performed on the testing dataset with an ACC of 0.750. The results demonstrated that iASMP had an excellent predictive performance and was suitable for identifying potential ASMP. Furthermore, we also visualized the selected features and rationally explained the impact of individual features on the model output.

NFIC attenuates rheumatoid arthritis-induced inflammatory response in mice by regulating PTEN/SENP8 transcription.

OBJECTIVE: To explore whether nuclear factor I C (NFIC) alleviated inflammatory response of synovial fibroblasts (SFs) caused by rheumatoid arthritis (RA) by regulating transcription levels of phosphatase and tension homolog deleted on chromosome 10 (PTEN) and sentrin-specific protease 8 (SENP8). METHODS: NFIC, PTEN, and SENP8 levels in RASFs and normal SFs (NSFs) were measured by qRT-PCR and western blotting. The levels of Bax, Bcl-2, MMP-3, and MMP-13, as well as the content of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined in RASFs and NSFs using western blotting and ELISA. The binding of NFIC to promoter sequences of PTEN and SENP8 was predicted and verified. A mouse model of collagen-induced arthritis (CIA) was established and evaluated according to the degree of joint swelling and arthritis index. RESULTS: NFIC, PTEN, and SENP8 were downregulated in RASFs. RASFs had increased viability and MDA levels as well as decreased cell apoptosis and SOD content. NFIC was demonstrated to modulate the transcription of PTEN and SENP8 as their transcription factor. NFIC ameliorated the inflammatory response induced by RA in vivo by promoting the transcription of PTEN and SENP8. CONCLUSION: NFIC acted as a transcription factor to facilitate the transcription of PTEN and SENP8, thereby inducing apoptosis of RASFs and effectively attenuating inflammatory response in CIA mice.

Engineering white blood cell membrane-camouflaged nanocarriers for inflammation-related therapeutics.

White blood cells (WBCs) play essential roles against inflammatory disorders, bacterial infections, and cancers. Inspired by nature, WBC membrane-camouflaged nanocarriers (WBC-NCs) have been developed to mimic the "dynamic" functions of WBCs, such as transendothelial migration, adhesion to injured blood vessels, etc, which make them promising for diverse medical applications. WBC-NCs inherit the cell membrane antigens of WBCs, while still exhibiting the robust inflammation-related therapeutic potential of synthetic nanocarriers with excellent (bio)physicochemical performance. This review summarizes the proposed concept of cell membrane engineering, which utilizes physical engineering, chemical modification, and biological functionalization technologies to endow the natural cell membrane with abundant functionalities. In addition, it highlights the recent progress and applications of WBC-NCs for inflammation targeting, biological neutralization, and immune modulation. Finally, the challenges and opportunities in realizing the full potential of WBC-NCs for the manipulation of inflammation-related therapeutics are discussed.

Uterine artery embolization combined with ultrasound-guided dilation and curettage for the treatment of cesarean scar pregnancy: Efficacy and 5-8-year follow-up study.

Objective: To evaluate the efficacy and safety of uterine artery embolization (UAE) combined with dilation and curettage (D&C) using ultrasound as a treatment for cesarean scar pregnancy (CSP) and assess its effect on ovarian and reproductive function. Methods: A total of 54 patients with uterine CSP between January 2011 and December 2015 were included in this retrospective study. The patients were treated with UAE combined with D&C using ultrasound for the treatment of CSP and followed up for 5-8 years. Their medical records, medical histories, clinical manifestations, treatment courses, and treatment results were analyzed. Results: The 54 patients were initially treated without severe complications. ß-Human chorionic gonadotropin (ß-hCG) normalization took 36.11 â€‹± â€‹10.73 days (range, 25-84 days), length of hospitalization was 6.6 â€‹± â€‹1.5 days (range, 4-10 days), and total blood loss was 18.48 â€‹± â€‹8.41 â€‹mL (range, 5-33 â€‹mL). All patients resumed normal menstruation after 33.48 â€‹± â€‹8.71 days (range, 26-70 days). At the 5-8-year follow-up after UAE combined with D&C by ultrasound for the treatment of uterine CSP, the menstrual volume in 32 (59.3%) patients decreased versus before the operation. Compared with pretreatment, the menstrual cycle was prolonged in two (3.7%) cases, shortened in 10 (18.5%) cases, irregular in one (1.9%) case, and unchanged in 39 (72.2%) cases. Three patients conceived naturally and successfully gave birth to healthy children. Seven (12.96%) patients with accidental natural pregnancies chose induced abortion with no significant change in their sex lives. Conclusion: UAE combined with D&C using ultrasound for the treatment of uterine CSP is safe and effective and may not affect the fertility of patients aged <40 years. However, menstrual volume may be reduced in some patients.

Extended endoscopic endonasal approach for resecting anterior intrinsic third ventricular craniopharyngioma.

Background: The surgical treatment of the extended endoscopic endonasal approach (EEEA) is a safe and effective treatment for suprasellar craniopharyngiomas. However, due to damage to the hypothalamus and third ventricle floor (TVF), EEEA is generally regarded as unsuitable in treating intrinsic third ventricle craniopharyngioma (ITVC) that is entirely within the third ventricle. Until now, there have been only a small number of reports using EEEA to treat TVC via a supra-infrachiasmatic approach. Given that the translamina terminalis (TLT) corridor was used in the transcranial subfrontal approach, EEEA via a suprachiasmatic approach may be feasible and practical to treat ITVC. In the current study, we accumulated experience applying the suprachiasmatic translamina terminalis (STLT) corridor for anterior treatment of ITVC. Methods: From March 2016 to December 2020, 14 patients with ITVC in our center were analyzed retrospectively. All patients underwent surgery by EEEA via an STLT corridor. The multilayer reconstruction technique was adopted to achieve skull base reconstruction. Data concerning the patient's tumor resection, vision, hypophyseal hormone, and complications were collected. Results: Gross-total resection was achieved in 13 (92.8%) of14 patients, with achievement of near-total (90%) resection in the remaining 1 patient. Nine cases (64.3%) were papillary craniopharyngiomas, and the other 5 cases were adamantinomatous subtypes. Postoperatively, 3 patients with pituitary insufficiency received hormone replacement therapy. No permanent diabetes insipidus or hypothalamic obesity was found. All pairs showed significant improvement or stability in vision except 1 patient who encountered visual deterioration. No other neurological deficit occurred postoperatively. Observation results for the exudation of nasal tissue and the length of hospitalization were satisfactory. After a mean follow-up period of 26.2 months, tumor recurrence was not observed. Conclusion: TLT is a minimally invasive corridor used in EEEA for treating anterior ITVC without increasing risks of visual and hormonal deficits. The multilayered reconstruction technique we used is a safe and effective method for achieving watertight closure and avoiding cerebrospinal fluid leaks and infection. The endonasal approach via STLT provides a new, safe and efficacious operative strategy that should be considered a surgical alternative in treating ITVC.

Osmoregulation determines sperm cell geometry and integrity for double fertilization in flowering plants.

Distinct from the motile flagellated sperm of animals and early land plants, the non-motile sperm cells of flowering plants are carried in the pollen grain to the female pistil. After pollination, a pair of sperm cells are delivered into the embryo sac by pollen tube growth and rupture. Unlike other walled plant cells with an equilibrium between internal turgor pressure and mechanical constraints of the cell walls, sperm cells wrapped inside the cytoplasm of a pollen vegetative cell have only thin and discontinuous cell walls. The sperm cells are uniquely ellipsoid in shape, although it is unclear how they maintain this shape within the pollen tubes and after release. In this study, we found that genetic disruption of three endomembrane-associated cation/H+ exchangers specifically causes sperm cells to become spheroidal in hydrated pollens of Arabidopsis. Moreover, the released mutant sperm cells are vulnerable and rupture before double fertilization, leading to failed seed set, which can be partially rescued by depletion of the sperm-expressed vacuolar water channel. These results suggest a critical role of cell-autonomous osmoregulation in adjusting the sperm cell shape for successful double fertilization in flowering plants.

Cell membrane-camouflaged inorganic nanoparticles for cancer therapy.

Inorganic nanoparticles (INPs) have been paid great attention in the field of oncology in recent past years since they have enormous potential in drug delivery, gene delivery, photodynamic therapy (PDT), photothermal therapy (PTT), bio-imaging, driven motion, etc. To overcome the innate limitations of the conventional INPs, such as fast elimination by the immune system, low accumulation in tumor sites, and severe toxicity to the organism, great efforts have recently been made to modify naked INPs, facilitating their clinical application. Taking inspiration from nature, considerable researchers have exploited cell membrane-camouflaged INPs (CMCINPs) by coating various cell membranes onto INPs. CMCINPs naturally inherit the surface adhesive molecules, receptors, and functional proteins from the original cell membrane, making them versatile as the natural cells. In order to give a timely and representative review on this rapidly developing research subject, we highlighted recent advances in CMCINPs with superior unique merits of various INPs and natural cell membranes for cancer therapy applications. The opportunity and obstacles of CMCINPs for clinical translation were also discussed. The review is expected to assist researchers in better eliciting the effect of CMCINPs for the management of tumors and may catalyze breakthroughs in this area.