Owing to their unique, nanoscale related optical properties, nanostructures assembled from molecular photosensitizers (PSs) have interesting applications in phototheranostics. However, most ...nanostructured PS assemblies are super‐quenched, thus, preventing their use in photodynamic therapy (PDT). Although some of these materials undergo stimuli‐responsive disassembly, which leads to partial recovery of PDT activity, their therapeutic potentials are unsatisfactory owing to a limited ability to promote generation reactive oxygen species (ROS), especially via type I photoreactions (i.e., not by 1O2 generation). Herein we demonstrate that a new, nanostructured phthalocyanine assembly, NanoPcA, has the ability to promote highly efficient ROS generation via the type I mechanism. The results of antibacterial studies demonstrate that NanoPcA has potential PDT applications.
Photodynamic nanodots self‐assembled from phthalocyanine molecules (NanoPcA) display highly efficient reactive oxygen species generation via a type I mechanism. Antibacterial studies demonstrate that NanoPcA has potential photodynamic therapy applications.
The combination of transition‐metal catalysis and organocatalysis increasingly offers chemists opportunities to realize diverse unprecedented chemical transformations. By combining iridium with ...chiral thiourea catalysis, direct enantioselective reductive cyanation and phosphonylation of secondary amides have been accomplished for the first time for the synthesis of enantioenriched chiral α‐aminonitriles and α‐aminophosphonates. The protocol is highly efficient and enantioselective, providing a novel route to the synthesis of optically active α‐functionalized amines from the simple, readily available feedstocks. In addition, the reactions are scalable and the thiourea catalyst can be recycled and reused.
The first enantioselective reductive cyanation and phosphonylation of secondary amides have been achieved by the combination of iridium with chiral thiourea catalysis. The protocol is highly efficient and enantioselective, providing a novel route for the synthesis of optically active α‐aminonitriles and α‐aminophosphonates from bench‐stable feedstocks.
Rechargeable potassium-ion batteries have been gaining traction as not only promising low-cost alternatives to lithium-ion technology, but also as high-voltage energy storage systems. However, their ...development and sustainability are plagued by the lack of suitable electrode materials capable of allowing the reversible insertion of the large potassium ions. Here, exploration of the database for potassium-based materials has led us to discover potassium ion conducting layered honeycomb frameworks. They show the capability of reversible insertion of potassium ions at high voltages (~4 V for K
Ni
TeO
) in stable ionic liquids based on potassium bis(trifluorosulfonyl) imide, and exhibit remarkable ionic conductivities e.g. ~0.01 mS cm
at 298 K and ~40 mS cm
at 573 K for K
Mg
TeO
. In addition to enlisting fast potassium ion conductors that can be utilised as solid electrolytes, these layered honeycomb frameworks deliver the highest voltages amongst layered cathodes, becoming prime candidates for the advancement of high-energy density potassium-ion batteries.
Bone cancer pain (BCP) is a clinical pathology that urgently needs to be solved, but research on the mechanism of BCP has so far achieved limited success. Nuclear factor erythroid 2 (NFE2)‐related ...factor 2 (Nrf2) has been shown to be involved in pain, but its involvement in BCP and the specific mechanism have yet to be examined. This study aimed to test the hypothesis that BCP induces the transfer of Nrf2 from the cytoplasm to the nucleus and further promotes nuclear transcription to activate heme oxygenase‐1 (HO‐1) and inhibit the activation of nuclear factor‐kappa B (NF‐κB) signalling, ultimately regulating the neuroinflammatory response. Von‐Frey was used for behavioural analysis in rats with BCP, whereas western blotting, real‐time quantitative PCR (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA) were used to detect molecular expression changes, and immunofluorescence was used to detect cellular localization. We demonstrated that BCP induced increased Nrf2 nuclear protein expression with decreased cytoplasmic protein expression in the spinal cord. Further increases in Nrf2 nuclear protein expression can alleviate hyperalgesia and activate HO‐1 to inhibit the expression of NF‐κB nuclear protein and inflammatory factors. Strikingly, intrathecal administration of the corresponding siRNA reversed the above effects. In addition, the results of double immune labelling revealed that Nrf2 and NF‐κB were coexpressed in spinal cord neurons of rats with BCP. In summary, these findings suggest that the entry of Nrf2 into the nucleus promotes the expression of HO‐1, inhibiting activation of the NF‐κB signalling pathway, reducing neuroinflammation and ultimately exerting an anti‐nociceptive effect.
We propose that Nrf2 (Nuclear factor erythroid 2 (NFE2)‐related factor 2) regulates NF‐κB (Nuclear factor‐kappa B) activation to attenuate neuroinflammation and bone cancer pain (BCP): Bone cancer–induced oxidative stress drives the dissociation of Nrf2 with Keap‐1 (kelch‐like ECH‐related protein 1) and transcription to the nucleus in spinal cord neurons, thereby initiating the body's defence response. Further promoting Nrf2 entry into the nucleus could increase HO‐1 (heme oxygenase‐1) expression to inhibit NF‐κB activation and downstream inflammatory factor release in spinal cord neurons and finally reduce pain. We believe that these findings can help provide new therapeutic strategies for the treatment of BCP.
Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress ...to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.
From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.
Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.
LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Despite significant progress, there remain three limitations to the previous multi-view clustering algorithms. First, they often suffer from high computational complexity, restricting their ...feasibility for large-scale datasets. Second, they typically fuse multi-view information via one-stage fusion, neglecting the possibilities in multi-stage fusions. Third, dataset-specific hyperparameter-tuning is frequently required, further undermining their practicability. In light of this, we propose a fast m ulti-v i ew c lustering via e nsembles (FastMICE) approach. Particularly, the concept of random view groups is presented to capture the versatile view-wise relationships, through which the hybrid early-late fusion strategy is designed to enable efficient multi-stage fusions. With multiple views extended to many view groups, three levels of diversity (w.r.t. features, anchors, and neighbors, respectively) are jointly leveraged for constructing the view-sharing bipartite graphs in the early-stage fusion. Then, a set of diversified base clusterings for different view groups are obtained via fast graph partitioning, which are further formulated into a unified bipartite graph for final clustering in the late-stage fusion. Notably, FastMICE has almost linear time and space complexity, and is free of dataset-specific tuning. Experiments on 22 multi-view datasets demonstrate its advantages in scalability (for extremely large datasets), superiority (in clustering performance), and simplicity (to be applied) over the state-of-the-art. Code available: https://github.com/huangdonghere/FastMICE .
An efficient and reconfigurable rectifier circuit, with the capability of automatically switching from low-power to high-power operation mode, is presented in this paper. The new topology allows the ...rectifier to convert RF power to dc power efficiently over an extended input power range. The circuit consists of diodes as rectifying elements and of n-channel field effect transistor in a depletion mode acting as the automated switch. Without using an external dc source, the circuit directly uses the rectified output dc voltage to bias the transistor, allowing high conversion efficiency over a wide input power range. This results in a compact and self-contained circuit. A total of two prototypes optimized for near-field and far-field wireless power transfer systems are fabricated and the measured results show that the performance exceeds that of the conventional rectifier circuit, which can only stay efficient over a limited range of the input power. The proposed design can maintain more than 50% of conversion efficiency over more than 25-dB range of the input power, with peak efficiency of 88% and 80% for near-field and far-field rectifiers, respectively. A system-level validation also confirms the improvement of the proposed rectifier design.
Mitochondrial dysfunction during aging is a key factor that contributes to sarcopenia. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been increasingly recognized to regulate mitochondrial ...function. The present study aimed to investigate the role of Nrf2 in the development of frailty and sarcopenia during aging, and to demonstrate whether Nrf2 contributes to the maintenance of muscle mass and function by regulation of mitochondrial biogenesis and dynamics during the aging process.
Young (5–6 months), middle-aged (11-13 months), old (20–24 months) Nrf2−/− (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice were used in this study. Physical function of the mice in the 6 groups was assessed by grip strength test, four paw inverted hanging test, rotarod analysis, open field analysis, and treadmill endurance test. Muscle mass was measured by cross-sectional area (CSA) of tibialis anterior muscles and gastrocnemius muscle weight. The frailty status of the 25 old WT mice and 23 old KO mice were assessed based on the mouse frailty phenotype assessment. Expression levels of genes involved in mitochondrial biogenesis (nuclear respiratory factor 1 (Nrf1), peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM)) and mitochondrial dynamics (optic atrophy protein 1 (Opa1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and dynamin-related protein 1 (Drp1)) were measured in the skeletal muscle. SDH staining was performed and mitochondrial DNA (mtDNA) copy number was measured. Transmission electron microscopy was used to measure the mitochondria number and morphology.
Physical function and muscle mass decreased during aging. The mRNA expression levels of Nrf2 decreased with increasing frailty phenotype scores in the old WT mice. There were minimal differences in the physical function and muscle mass between the WT and KO mice in the young groups, whereas Nrf2 deficiency caused a declined physical function and muscle mass in the middle-aged and old mice, and exacerbated frailty in the old mice. The decreases of the physical function and muscle mass were accompanied by the reduced expression levels of genes involved in mitochondrial biogenesis and dynamics, as well as a reduction of mitochondrial number, mitochondrial content, mtDNA copy number, and an impaired mitochondria morphology in the skeletal muscle.
Nrf2 deficiency exacerbated frailty and sarcopenia during aging, at least partially by impairing skeletal muscle mitochondrial biogenesis and dynamics in an age-dependent manner.
•Muscle mass/function and mitochondrial homeostasis are impaired during aging in mice.•Decline of muscle mass/function is linked with mitochondrial dysfunction during aging.•Nrf2 deficiency has few effect on frailty/sarcopenia and mitochondria in young mice.•Nrf2 deficiency worsens mitochondrial dysfunction, frailty/sarcopenia in older mice.
Background The association between sarcopenia and postoperative outcomes has been well reported. However, the impact of different sarcopenia stages on postoperative outcomes has never been ...investigated. Methods We conducted a large, prospective study of patients who underwent radical gastrectomy for gastric cancer from August 2014 to December 2015. Sarcopenia was staged as “presarcopenia,” “sarcopenia,” and “severe sarcopenia” according to the definition of the European Working Group on Sarcopenia in Older People. Univariate and multivariate analyses evaluating the risk factors for total, surgical, and medical complications were performed. Results A total of 470 patients were included, in which 20.6%, 10%, and 6.8% of the patients were identified as having “presarcopenia,” “sarcopenia,” and “severe sarcopenia,” respectively. Postoperative complications, duration of hospital stays, and costs increased with advancing sarcopenia stages. Severe sarcopenia, visceral fat area to total abdominal muscle area ratio, American Society of Anesthesiologists grade III, and tumor located at the cardia were independent risk factors for total complications. Visceral fat area to total abdominal muscle area ratio and tumor located at the cardia were independent risk factors for operative complications. Presarcopenia, sarcopenia, and severe sarcopenia were all identified as independent risk factors for medical complications, as well as age ≥75 years and Charlson Comorbidity Index. Conclusion Patients had worse postoperative outcomes after gastric cancer operation with advancing sarcopenia stages. Severe sarcopenia, but not presarcopenia or sarcopenia, was an independent risk factor for total postoperative complications. The 3 sarcopenia stages independently influence medical but not surgical complications. Recognizing sarcopenia stages is important for preoperative risk stratification.
Globally, liver cancer, which is one of the major cancers worldwide, has attracted the growing attention of technological researchers for its high mortality and limited treatment options. Hydrogels ...are soft 3D network materials containing a large number of hydrophilic monomers. By adding moieties such as nitrobenzyl groups to the network structure of a cross‐linked nanocomposite hydrogel, the click reaction improves drug‐release efficiency in vivo, which improves the survival rate and prolongs the survival time of liver cancer patients. The application of a nanocomposite hydrogel drug delivery system can not only enrich the drug concentration at the tumor site for a long time but also effectively prevents the distant metastasis of residual tumor cells. At present, a large number of researches have been working toward the construction of responsive nanocomposite hydrogel drug delivery systems, but there are few comprehensive articles to systematically summarize these discoveries. Here, this systematic review summarizes the synthesis methods and related applications of nanocomposite responsive hydrogels with actions to external or internal physiological stimuli. With different physical or chemical stimuli, the structural unit rearrangement and the controlled release of drugs can be used for responsive drug delivery in different states.
Cross‐linked hydrophilic polymer chains that can form gels are widely utilized for biomedical applications, such as drug delivery. Various studies have also demonstrated the effects of particle size and surface morphology on drug release from particles in liver cancer therapy. Mechanistic understandings of responsive hydrogels in responsive stimuli are provided, by which better clinical choices may be approached.
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