With the ever‐increasing threat posed by the multi‐drug resistance of bacteria, the development of non‐antibiotic agents for the broad‐spectrum eradication of clinically prevalent superbugs remains a ...global challenge. Here, we demonstrate the simple supramolecular self‐assembly of structurally defined graphene nanoribbons (GNRs) with a cationic porphyrin (Pp4N) to afford unique one‐dimensional wire‐like GNR superstructures coated with Pp4N nanoparticles. This Pp4N/GNR nanocomposite displays excellent dual‐modal properties with significant reactive‐oxygen‐species (ROS) production (in photodynamic therapy) and temperature elevation (in photothermal therapy) upon light irradiation at 660 and 808 nm, respectively. This combined approach proved synergistic, providing an impressive antimicrobial effect that led to the complete annihilation of a wide spectrum of Gram‐positive, Gram‐negative, and drug‐resistant bacteria both in vitro and in vivo. The study also unveils the promise of GNRs as a new platform to develop dual‐modal antimicrobial agents that are able to overcome antibiotic resistance.
Antibacterial steamroller: Polycationic porphyrin and water‐dispersible graphene nanoribbons self‐assemble into a supramolecular nanocomposite that combines both photodynamic and photothermal therapy for the treatment of bacterial infections. The nanocomposite exhibits an impressive antimicrobial activity that leads to the complete annihilation of a wide spectrum of Gram‐positive, Gram‐negative, and drug‐resistant bacteria.
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.
Human beings are “machines” that use endogenously produced biomolecules as “components” in signaling and for the maintenance of the body. These biomolecules consist of proteins, nucleic acids, and ...carbohydrates, which can either be extracted from biological substrates or synthesized by chemical/biochemical methods. These biomolecules have the ability to recognize/interact with other biomolecules that are overexpressed in disease cells. For targeted theranostics, strategies to chemically incorporate these natural biomolecules with advanced materials to treat human diseases by imaging‐guided drug delivery or photodynamic/photothermal therapy are proposed, with improved biocompatibility. Herein, recent research on construction of quantum dots, nanoparticles, and 2D material platforms decorated with antibodies, peptides, nucleic acid aptamers, carbohydrates, and folic acid for targeted diagnosis and treatment are summarized and discussed. In addition, the various strategies required to construct effective functional materials for targeted cancer therapy are highlighted. The hope is that this review can inspire and guide those that are interested in the field of biomedicine to rationally design and develop new target‐based theranostic materials.
Recent research progress on the construction of quantum dots, inorganic nanoparticles, conjugated polymers, and 2D material platforms decorated with antibodies, peptides, nucleic acid aptamers, carbohydrates, and folic acid for targeted diagnosis and treatment are summarized and discussed. In addition, the various strategies required to construct effective functional materials for targeted cancer therapy are highlighted.
With the evergrowing threat posed by multidrug resistance of bacteria, the development of effective antibacterial agents remains a global challenge. Infection with multidrug‐resistant bacteria in ...hospitals significantly impairs the healing of wounds caused by deep‐burn injuries or diabetic foot ulceration, leading to a high mortality rate among these patients. A multivalent glycosheet for the double light–driven therapy against multidrug‐resistant Pseudomonas aeruginosa (P. aeruginosa) infection on wounds is developed here. Galactose‐ and fucose‐based ligands are self‐assembled to form a glyco‐layer on the surface of thin‐layer molybdenum disulfide, producing the glycosheets capable of selectively localizing P. aeruginosa through multivalent carbohydrate–lectin interactions. The glycosheets loaded with antibiotics have proven applicable for: 1) near‐infrared‐light driven, in situ thermal release of antibiotics, increasing bacterial membrane permeability, and 2) white light–driven reactive‐oxygen‐species production to more thoroughly kill the bacteria. The targetability, together with the light sensibility, of the glycosheets enables a highly effective and optically controlled therapeutic regime for the healing of wounds infected by multidrug‐resistant as well as clinically isolated P. aeruginosa.
A multivalent, double light–driven glycosheet is developed for the effective killing of multidrug‐resistant, clinically isolated P. Aeruginosa on wounds.
In a previous phase II trial, hepatic arterial infusion chemotherapy (HAIC) with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) yielded higher treatment responses than transarterial ...chemoembolization (TACE) in large unresectable hepatocellular carcinoma. We aimed to compare the overall survival of patients treated with FOLFOX-HAIC versus TACE as first-line treatment in this population.
In this randomized, multicenter, open-label trial, adults with unresectable hepatocellular carcinoma (largest diameter ≥ 7 cm) without macrovascular invasion or extrahepatic spread were randomly assigned 1:1 to FOLFOX-HAIC (oxaliplatin 130 mg/m
, leucovorin 400 mg/m
, fluorouracil bolus 400 mg/m
on day 1, and fluorouracil infusion 2,400 mg/m
for 24 hours, once every 3 weeks) or TACE (epirubicin 50 mg, lobaplatin 50 mg, and lipiodol and polyvinyl alcohol particles). The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received ≥ 1 cycle of study treatment.
Between October 1, 2016, and November 23, 2018, 315 patients were randomly assigned to FOLFOX-HAIC (n = 159) or TACE (n = 156). The median overall survival in the FOLFOX-HAIC group was 23.1 months (95% CI, 18.5 to 27.7) versus 16.1 months (95% CI, 14.3 to 17.9) in the TACE group (hazard ratio, 0.58; 95% CI, 0.45 to 0.75;
< .001). The FOLFOX-HAIC group showed a higher response rate than the TACE group (73 46%
28 18%;
< .001) and a longer median progression-free survival (9.6 95% CI, 7.4 to 11.9
5.4 months 95% CI, 3.8 to 7.0,
< .001). The incidence of serious adverse events was higher in the TACE group than in the FOLFOX-HAIC group (30%
19%,
= .03). Two deaths in the FOLFOX-HAIC group and two in the TACE group were deemed to be treatment-related.
FOLFOX-HAIC significantly improved overall survival over TACE in patients with unresectable large hepatocellular carcinoma.
•The biological importance of lipid droplets (LDs).•Brief introduction to the formation and physiological functions of LDs.•Recent examples of LD-based fluorescent probes.•The various fluorescence ...mechanisms exploited to create LD probes.
Lipid droplets (LDs) are cellular organelles that are essential for maintaining lipid and energy homeostasis. Once regarded as merely inert fat particles, they are now recognized as highly dynamic, mobile organelles required for preventing lipotoxicity and for interacting and cooperating with various organelles. Despite the progress made in understanding the role of LDs, a number of fundamental questions remain unanswered. Effective imaging agents for observing the morphology and dynamic physiological processes of LDs in cells could help address this knowledge gap. Such probes are expected to aid in our understanding of LDs and facilitate the development of new and effective therapeutics. In this review, we have provided a brief introduction to the formation and physiological functions of LDs in an attempt to highlight the importance of these underappreciated organelles. Recent examples of LD-based fluorescent probes are discussed, including the fluorescence phenomenon used in their design. To date, both intramolecular charge transfer (ICT) and aggregation-induced emission (AIE) fluorescence mechanisms have been exploited to create LD probes. However, alternative strategies can be envisioned. We hope the readers will be enlightened as to the importance of these key organelles, will be poised to exploit existing probes to explore various biological applications, and be inspired to create new LD fluorescent sensors that will further our understanding of LDs and their associated physiology.
A 2D “glycosheet” based on supramolecular self‐assembly between 2D MoS2 and fluorescent glycoligands is developed. The composite 2D material is proven suitable for targeted intracellular production ...of reactive oxygen species (singlet oxygen) by the sequential control of a receptor endocytosis and light irradiation.
Psychogenic non-epileptic seizures (PNES) are paroxysmal behaviors that resemble epileptic seizures but lack abnormal electrical activity. Recent studies suggest aberrant functional connectivity ...involving specific brain regions in PNES. Little is known, however, about alterations of topological organization of whole-brain functional and structural connectivity networks in PNES. We constructed functional connectivity networks from resting-state functional MRI signal correlations and structural connectivity networks from diffusion tensor imaging tractography in 17 PNES patients and 20 healthy controls. Graph theoretical analysis was employed to compute network properties. Moreover, we investigated the relationship between functional and structural connectivity networks. We found that PNES patients exhibited altered small-worldness in both functional and structural networks and shifted towards a more regular (lattice-like) organization, which could serve as a potential imaging biomarker for PNES. In addition, many regional characteristics were altered in structural connectivity network, involving attention, sensorimotor, subcortical and default-mode networks. These regions with altered nodal characteristics likely reflect disease-specific pathophysiology in PNES. Importantly, the coupling strength of functional-structural connectivity was decreased and exhibited high sensitivity and specificity to differentiate PNES patients from healthy controls, suggesting that the decoupling strength of functional-structural connectivity might be an important characteristic reflecting the mechanisms of PNES. This is the first study to explore the altered topological organization in PNES combining functional and structural connectivity networks, providing a new way to understand the pathophysiological mechanisms of PNES.
An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide ...attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.
It is unclear whether the magnitude and duration of elevated central venous pressure (ECVP) greater than ten mmHg has the same impact on mortality in sepsis patients.
Critically ill patients with ...sepsis were identified from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The duration and the magnitude of ECVP were calculated. Normalized ECVP load was defined as the ECVP load (the sum of ECVP value times its duration) divided by the total duration of ECVP. The primary endpoint was 28-day mortality. Kaplan-Meier survival analysis was used to compare survival between patients with high or low normalized ECVP load.
A total of 1071 sepsis patients were included. Higher normalized ECVP load was associated with higher mortality rate; in contrast, the duration of ECVP was not associated with mortality. A linear relationship between normalized ECVP load and mortality was identified. Patients with higher normalized ECVP load had less urine output and more positive fluid balance.
The magnitude, but not the duration of ECVP, is associated with mortality in sepsis patients. ECVP should be considered as a valuable and easily accessible safety parameter during fluid resuscitation.
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