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AbstractRemaining useful life (RUL) prediction is an essential tool for enhancing the reliability and resilience of systems. Most existing RUL prediction methods consider degradation-induced failures, and assume there exists a fixed failure threshold for degradation signals. In many real applications, however, it is difficult or even impossible to find such failure thresholds, making the RUL prediction a challenging task. This study addresses the challenge by exploiting the method of forward intensity, a novel tool introduced in econometrics. In particular, the historical degradation signals are treated as time-varying covariates for the forward intensity. The dynamics of unobserved future degradation signals are captured by a time-varying regression parameter in the forward intensity function, which are usually estimated using the maximum pseudolikelihood method in existing studies. To improve prediction accuracy, this study proposes a new estimation method based on smoothing splines. The proposed method not only allows RUL prediction in the absence of a fixed failure threshold, but also achieves satisfactory prediction accuracy with reasonable interpretability of covariate effects. Prediction intervals for the RUL are also developed. The effectiveness of the proposed method is validated through Monte Carlo simulations and three real-data examples. The results show that the proposed method outperforms existing methods in terms of prediction accuracy. [ABSTRACT FROM AUTHOR]

Objectives: Circular RNAs (circRNAs) serve a crucial regulatory role in ovarian cancer (OC). Circular RNA ArfGAP with FG repeats 1 (circAGFG1) has been shown to be involved in promoting the progression of several cancers, containing triple-negative breast cancer, esophageal cancer and colorectal cancer. However, the function of circAGFG1 in OC is unclear. Methods: Quantitative real-time reverse transcription PCR (RT-qPCR) was conducted to determine the expression levels of circAGFG1 and miR-409-3p. The proliferation and metastasis of cells were determined by colony formation assays, EdU assays, transwell assays and wound healing assays. In addition, a dual-luciferase reporter assay was performed to validate the mechanism between circAGFG1, miR-409-3p, and ZEB1. Results: Our data suggested that circAGFG1 was significantly overexpressed in OC tissues compared to normal ovarian epithelial tissues. Overexpression of circAGFG1 was correlated with intraperitoneal metastasis, tumor recurrence and advanced stage. Additionally, circAGFG1 overexpression revealed a poor prognosis in OC patients. Knockdown of circAGFG1 suppressed the proliferation, invasion and migration of OC cells. Mechanistically, circAGFG1 acted as a sponge of miR-409-3p to enhance the expression level of zinc finger E-box binding homeobox 1 (ZEB1), thereby conferring OC cell proliferation, invasion and migration. Importantly, re-expression of ZEB1 effectively reversed the effects of circAGFG1 knockdown on OC cells. Conclusions: In summary, our study indicated that circAGFG1 may act as a prognostic biomarker and potential therapeutic target for patients with OC. [ABSTRACT FROM AUTHOR]

Rapid wound dressing and effective antibacterial therapy that meet the extreme requirements of emergency situations are urgently needed for treating skin wounds. Here, an in situ deposited and personalized nanofibrous dressing is reported which can be directly electrospun on skin wounds by a handheld electrospinning device and perfectly fits different wounds of various sizes. Moreover, an aggregation‐induced emission luminogen with photodynamic therapy effect is loaded in the nanofibrous dressings which endows the dressing's long‐term antibacterial activity during the wound healing process. The in situ electrospun nanofibers show excellent antimicrobial activity against Staphylococcus aureus (S. aureus) and methicillin‐resistant Staphylococcus aureus. In vivo studies demonstrate that these antibacterial nanofibrous dressings can effectively reduce inflammation and significantly accelerate wound healing. Such an in situ produced antibacterial dressing is promising as a total solution for treating emergencies, including patient‐specific clinical wounds and military injuries. [ABSTRACT FROM AUTHOR]

Photo-driven theranostics, also known as phototheranostics, relying on the diverse excited-state energy conversions of theranostic agents upon photoexcitation represents a significant branch of theranostics, which ingeniously integrate diagnostic imaging and therapeutic interventions into a single formulation. The combined merits of photoexcitation and theranostics endow photo-driven theranostics with numerous superior features. The applications of aggregation-induced emission luminogens (AIEgens), a particular category of fluorophores, in the field of photo-driven theranostics have been intensively studied by virtue of their versatile advantageous merits of favorable biocompatibility, tuneable photophysical properties, unique aggregation-enhanced theranostic (AET) features, ideal AET-favored on-site activation ability and ready construction of one-for-all multimodal theranostics. This review summarised the significant achievements of photo-driven theranostics based on AIEgens, which were detailedly elaborated and classified by their diverse theranostic modalities into three groups: fluorescence imaging-guided photodynamic therapy, photoacoustic imaging-guided photothermal therapy, and multi-modality theranostics. Particularly, the tremendous advantages and individual design strategies of AIEgens in pursuit of high-performance photosensitizing output, high photothermal conversion and multimodal function capability by adjusting the excited-state energy dissipation pathways are emphasized in each section. In addition to highlighting AIEgens as promising templates for modulating energy dissipation in the application of photo-driven theranostics, current challenges and opportunities in this field are also discussed. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) bacteria pose a serious threat to human health. The development of alternative treatment modalities and therapeutic agents for treating MDR bacteria‐caused infections remains a global challenge. Herein, a series of near‐infrared (NIR) anion–π+ photosensitizers featuring aggregation‐induced emission (AIE‐PSs) are rationally designed and successfully developed for broad‐spectrum MDR bacteria eradication. Due to the strong intramolecular charge transfer (ICT) and enhanced highly efficient intersystem crossing (ISC), these electron‐rich anion–π+ AIE‐PSs show boosted type I reactive oxygen species (ROS) generation capability involving hydroxyl radicals and superoxide anion radicals, and up to 99% photodynamic killing efficacy is achieved for both Methicillin‐resistant Staphylococcus aureus (MRSA) and multidrug resistant Escherichia coli (MDR E. coli) under a low dose white light irradiation (16 mW cm−2). In vivo experiments confirm that one of these AIE‐PSs exhibit excellent therapeutic performance in curing MRSA or MDR E. coli‐infected wounds with negligible side‐effects. The study would thus provide useful guidance for the rational design of high‐performance type I AIE‐PSs to overcome antibiotic resistance. [ABSTRACT FROM AUTHOR]

Bacteria infected cells acting as "Trojan horses" not only protect bacteria from antibiotic therapies and immune clearance, but also increase the dissemination of pathogens from the initial sites of infection. Antibiotics are hard and insufficient to treat such hidden internalized bacteria, especially multidrug‐resistant (MDR) bacteria. Herein, aggregation‐induced emission luminogens (AIEgens) such as N,N‐diphenyl‐4‐(7‐(pyridin‐4‐yl) benzo [c] [1,2,5] thiadiazol‐4‐yl) aniline functionalized with 1‐bromoethane (TBP‐1) and (3‐bromopropyl) trimethylammonium bromide (TBP‐2) (TBPs) show potent broad‐spectrum bactericidal activity against both extracellular and internalized Gram‐positive pathogens. TBPs trigger reactive oxygen species (ROS)‐mediated membrane damage to kill bacteria, regardless of light irradiation. TBPs effectively kill bacteria without the development of resistance. Additionally, such AIEgens activate mitochondria dependent autophagy to eliminate internalized bacteria in host cells. Compared to the routinely used vancomycin in clinic, TBPs demonstrate comparable efficacy against methicillin‐resistant Staphylococcus aureus (MRSA) in vivo. The studies suggest that AIEgens are promising new agents for the treatment of MDR bacteria associated infections. [ABSTRACT FROM AUTHOR]

Bacterial infections pose a serious threat to human health. Photodynamic therapy is an effective medical treatment to solve the problems raised by antibiotic resistant bacteria. But it is not easy to have photosensitizers (PSs) that can simultaneously produce efficient fluorescence and reactive oxygen species. Traditional PSs show compromised performances due to the aggregation‐caused quenching effect in aqueous media, however, luminogens with aggregation‐induced emission (AIE) can inherently achieve high fluorescence and efficient ROS generation. In addition, electrostatic interaction is generally accepted to be responsible for initial targeting of bacteria. But for AIE PSs, the roles of molecular charges on antibacterial efficiency are rarely considered. Herein, two red‐emissive AIE PSs with the same luminogenic core but carrying different number of positive charges are designed, and their antibacterial performance and the killing mechanism toward Gram‐positive (G(+)) and Gram‐negative (G(−)) bacteria are investigated. The AIE PSs with highly efficient singlet oxygen generation can clearly image and selectively kill bacteria over mammalian cells. With the increase in the positive charges of AIE PSs, the improvement in antibacterial efficiency is great against G(−) bacteria, but it is negligible against G(+) bacteria. This research will provide new insight into the rational design of new antibacterial materials. [ABSTRACT FROM AUTHOR]

Disilanes possessing a Si−Si bond are unique element–element species. Transition‐metal‐catalyzed activation of the Si−Si bond allows many useful transformations that generate diverse organosilanes. This Minireview highlights impressive developments in this field over the past decade, with an emphasis on the formation of vinyl‐, aryl‐, and acylsilanes by C(sp2)−Si bond formation as well as the formation of allyl‐ and alkylsilanes by C(sp3)−Si bond formation. Si‐gn of the times: Transition‐metal‐catalyzed activation of the Si−Si bond allows many useful transformations that generate diverse organosilanes. This Minireview highlights impressive developments in this field over the past decade, with an emphasis on the formation of vinyl‐, aryl‐, and acylsilanes by C(sp2)−Si bond formation as well as the formation of allyl‐ and alkylsilanes by C(sp3)−Si bond formation. NPhth=phthalimido, Q=8‐quinolinyl. [ABSTRACT FROM AUTHOR]

Abstract: The air‐stable unsymmetrical disilane Me3Si−SiMe2[oCON(iPr)2C6H4] has been developed for bis‐silylation of alkynes. This reagent tolerates a range of functional groups, providing Z‐vinyl disilanes in high yields. It is proposed that the phenyl‐ring‐tethered amide group directs oxidative addition of Pd0 into the Si−Si bond, which might facilitate formation of a six‐membered Pd cycle, generating products with good to excellent regioselectivity. [ABSTRACT FROM AUTHOR]

Intriguingly, TBPs promote mitochondria dependent autophagy to eliminate such bacteria in host cells. In article number 2001750, Kui Zhu, Ben Zhong Tang and co-workers demonstrate that aggregationinduced emission luminogens such as TBPs trigger ROS-mediated membrane damage to effectively kill internalized bacteria without resistance development. Targeting Multidrug-Resistant Bacteria: Efficient Killing of Multidrug-Resistant Internalized Bacteria by AIEgens In Vivo (Adv. Sci. 9/2021). [Extracted from the article]

Tumor metastasis is an intricate multistep process regulated via various proteins and enzymes modified and secreted by swollen Golgi apparatus in tumor cells. Thus, Golgi complex is considered as an important target for the remedy of metastasis. Currently, Golgi targeting technologies are mostly employed in Golgi-specific fluorescent probes for diagnosis, but their applications in therapy are rarely reported. Herein, we proposed a prodrug (INR) that can target and destroy the Golgi apparatus, which consisted of indomethacin (IMC) as the Golgi targeting moiety and retinoic acid (RA), a Golgi disrupting agent. The linker between IMC and RA was designed as a hypoxia-responsive nitroaromatic structure, which ensured the release of the prototype drugs in the hypoxic tumor microenvironment. Furthermore, INR could be assembled with pirarubicin (THP), an anthracycline, to form a carrier-free nanoparticle (NP) by emulsion-solvent evaporation method. A small amount of mPEG 2000 -DSPE was added to shield the positive charges and improve the stability of the nanoparticle to obtain PEG-modified nanoparticle (PNP). It was proved that INR released the prototype drugs in tumor cells and hypoxia promoted the release. The Golgi destructive effect of RA in INR was amplified owing to the Golgi targeting ability of IMC, and IMC also inhibited the protumor COX-2/PGE 2 signaling. Finally, PNP exhibited excellent curative efficacy on 4T1 primary tumor and its pulmonary and hepatic metastasis. The small molecular therapeutic prodrug targeting Golgi apparatus could be adapted to multifarious drug delivery systems and disease models, which expanded the application of Golgi targeting tactics in disease treatment.

Phototheranostics has received sustained attention due to its great potential in revolutionizing conventional strategies of cancer treatment. However, trapped by the complexity, poor reproducibility, insufficient phototheranostic outputs, and inevitable damage to normal tissue of most multicomponent phototheranostic systems, its clinical translation has been severely hindered. Therefore, the exploration of "one for all" smart phototheranostic agents with versatile functionalities remains an appealing yet enormously challenging task. Herein, a reversibly pH-switchable and near-infrared second photosensitizer featuring aggregation-induced emission was tactfully designed by molecular engineering for precise tumor-targeting fluorescence imaging-guided phototherapy. Thanks to the strong intramolecular charge transfer, enhanced highly efficient intersystem crossing, and sufficient intramolecular motion, the developed agent DTTVBI was endowed with boosted type-I superoxide anion radical generation and excellent photothermal performance under 808 nm laser irradiation. More importantly, DTTVBI nanoparticles with high biocompatibility exhibit remarkably enhanced type-I photodynamic/photothermal therapy in the tumor region, thus offering significant antitumor effects both in vitro and in the patient-derived tumor xenograft model of colon cancer. This work sheds new light on the development of superior versatile phototheranostics for cancer therapy.

Phototheranostics involving both fluorescence imaging and photodynamic therapy has been recognized to be potentially powerful for cancer treatment by virtue of various intrinsic advantages. However, the state-of-the-art materials in this area are still far from ideal toward practical applications, ascribed to their respective and collective drawbacks, such as inefficient imaging quality, inferior reactive oxygen species (ROS) production, the lack of subcellular-targeting capability, and dissatisfactory delivery. In this paper, these shortcomings are successfully addressed through the integration of finely engineered photosensitizers with aggregation-induced emission (AIE) features and well tailored nanocarrier systems. The yielded AIE NPs simultaneously exhibit broad absorption in the visible-light region, bright near-infrared fluorescence emission, high ROS generation, as well as tumor lysosomal acidity-activated and nucleus-targeted delivery functions, making them promising for precise and efficient phototheranostics. Both in vitro and in vivo evaluations show that the presented nanotheranostic systems bearing good photostability and appreciable biosecurity perform well in fluorescence imaging-guided photodynamic cancer therapy. This study thus not only extends the application scopes of AIE nanomaterials but also offers useful insights into constructing advanced cancer phototheranostics.

Background: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDA-approved PEG-liposomes of DOX for the treatment of over 600,000 cancer patients, and it can overcome doxorubicin-induced cardiomyopathy and other side effects and prolong life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment., Objective: We intended to prepare a novel DOX liposome that was prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical application., Methods: DOX liposomes were prepared using the combination of thin-film dispersion ultrasonic method and ammonium sulfate gradient method and the factors that influenced formulation quality were optimized. After formulation, particle size, entrapment efficiency, drug loading, stability, and pharmacokinetics were determined., Results: DOX liposomes were near-spherical morphology with the average size of 90 nm and polydispersity index (PDI) of less than 0.30. The drug loading was up to 7.5%, and the entrapment efficiency was over 80%. The pharmacokinetic studies showed that free DOX could be easily removed and the blood concentration of free DOX group was significantly lower than that of DOX liposomes, which indicated that the novel DOX liposome had a certain sustainedrelease effect., Conclusion: In summary, DOX liposome is economical and easy-prepared with prolonged circulation time. Lay Summary: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDAapproved PEG-liposomes of DOX to treat over 600.000 cancer patients, overcoming doxorubicin- induced cardiomyopathy and other side effects and prolonging life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. We intend to prepare a novel DOX liposome prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical use. The novel DOX liposome is economical and easy-prepared with prolonged circulation time., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The air-stable unsymmetrical disilane Me 3 Si-SiMe 2 [oCON(iPr) 2 C 6 H 4 ] has been developed for bis-silylation of alkynes. This reagent tolerates a range of functional groups, providing Z-vinyl disilanes in high yields. It is proposed that the phenyl-ring-tethered amide group directs oxidative addition of Pd 0 into the Si-Si bond, which might facilitate formation of a six-membered Pd cycle, generating products with good to excellent regioselectivity., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A sequential one-pot process for chemoselectively reducing sterically demanding N,N-diisopropylamides to aldehydes has been developed. In this reaction, amides are activated with EtOTf to form imidates, which are reduced with LiAlH(OR) 3 [R = t-Bu, Et] to give aldehydes by hydrolysis of the resulting hemiaminals. The non-nucleophilic base 2,6-DTBMP remarkably improves reaction efficiency. The combination of EtOTf/2,6-DTBMP and LiAlH(O-t-Bu) 3 was found to be optimal for reducing alkyl, alkenyl, alkynyl, and 2-monosubstituted aryl N,N-diisopropylamides. In contrast, EtOTf and LiAlH(OEt) 3 in the absence of base were found to be optimal for reducing extremely sterically demanding 2,6-disubstituted N,N-diisopropylbenzamides. The reaction tolerates various reducible functional groups, including aldehyde and ketone. 1 H NMR studies confirmed the formation of imidates stable in water. The synthetic usefulness of this methodology was demonstrated with N,N-diisopropylamide-directed ortho-metalation and C-H bond activation.

The unique steric effect of geminal bis(silane) [(R3Si)2CH] allows an exo-selective intermolecular Diels-Alder reaction of geminal bis(silyl) dienes with α,β-unsaturated carbonyl compounds. The approach shows good generality to form ortho-trans cyclohexenes in good yields with high exo-selectivity and high enantioselectivity in some asymmetric cases. The excellent exo-stereocontrol aptitude of (R3Si)2CH group is highlighted by comparing with R3SiCH2 and R3Si groups, which leads to endo-selectivity predominantly. The conformational analysis of dienes suggests that (R3Si)2CH group effectively shields both sides of the diene moiety, ensuring the desired exo-selectivity. Moreover, the geminal bis(silane) can be further functionalized to transform the resulting ortho-trans cycloadducts into useful synthons, which makes the approach hold great potential for organic synthesis.