Recent advances on thermosensitive hydrogels-mediated precision therapy

Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential.These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature.Inspired by their unique properties,thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine.In this review,the state-of-theart developments in thermosensitive hydrogels for precision therapy are investigated,which covers from the thermo-gelling mechanisms and main components to biomedical applications,including wound healing,anti-tumor activity,osteogenesis,and periodontal,sinonasal and ophthalmic diseases.The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.

Metal natural product complex Ru-procyanidins with quadruple enzymatic activity combat infections from drug-resistant bacteria

Bacterial infection hampers wound repair by impeding the healing process.Concurrently,inflammation at the wound site triggers the production of reactive oxygen species(ROS),causing oxidative stress and damage to proteins and cells.This can lead to chronic wounds,posing severe risks.Therefore,eliminating bacterial infection and reducing ROS levels are crucial for effective wound healing.Nanozymes,possessing enzyme-like catalytic activity,can convert endogenous substances into highly toxic substances,such as ROS,to combat bacteria and biofilms without inducing drug resistance.However,the current nanozyme model with single enzyme activity falls short of meeting the complex requirements of antimicrobial therapy.Thus,developing nanozymes with multiple enzymatic activities is essential.Herein,we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles(Ru-PC NPs)with diverse enzymatic activities to aid wound healing and combat bacterial infections.Under acidic conditions,due to their glutathione(GSH)depletion and peroxidase(POD)-like activity,Ru-PC NPs combined with H2O2 exhibit excellent antibacterial effects.However,in a neutral environment,the Ru-PC NPs,with catalase(CAT)activity,decompose H2O2 to O2,alleviating hypoxia and ensuring a sufficient oxygen supply.Furthermore,Ru-PC NPs possess exceptional antioxidant capacity through their superior superoxide dismutase(SOD)enzyme activity,effectively scavenging excess ROS and reactive nitrogen species(RNS)in a neutral environment.This maintains the balance of the antioxidant system and prevents inflammation.Ru-PC NPs also promote the polarization of macrophages from M1 to M2,facilitating wound healing.More importantly,Ru-PC NPs show good biosafety with negligible toxicity.In vivo wound infection models have confirmed the efficacy of Ru-PC NPs in inhibiting bacterial infection and promoting wound healing.The focus of this work highlights the quadruple enzymatic activity of Ru-PC NPs and its potential to reduce inflammation and promote bacteria-infected wound healing.

Upconversion nanoparticles@AgBiS_(2) core-shell nanoparticles with cancer-cell-specific cytotoxicity for combined photothermal and photodynamic therapy of cancers

UCNPs@AgBiS_(2) core-shell nanoparticles that AgBiS_(2) coated on the surface of upconversion nanoparticles (UCNPs) was successfully prepared through an ion exchange reaction. The photothermal conversion efficiency of AgBiS_(2) can be improved from 14.7% to 45% due to the cross relaxation between Nd ions and AgBiS_(2). The doping concentration of Nd ions played a critical role in the production of reactive oxygen species (ROS) and enhanced the photothermal conversion efficiency. The NaYF4:Yb/Er/Nd@NaYF4:Nd nanoparticles endows strong upcon-version emissions when the doped concentration of Nd ions is 1% in the inner core, which excites the AgBiS_(2) shell to produce ROS for photodynamic therapy (PDT) of cancer cells. As a result, the as-prepared NaYF4:Yb/Er/ Nd@NaYF4:Nd@AgBiS_(2) core-shell nanoparticles showed combined photothermal/photodynamic therapy (PTT/ PDT) against malignant tumors. This work provides an alternative near-infrared light-active multimodal nano-structures for applications such as fighting against cancers.

Antibacterial mechanism and transcriptomic analysis of a nearinfrared triggered upconversion nanoparticles@AgBiS2 for synergetic bacteria-infected therapy

Methicillin-resistant Staphylococcus aureus(MRSA)has become a rising clinical problem as its occurrence has increased due to the overuse and misuse of antibiotics.In this work,upconversion nanoparticles@AgBiS2 core–shell were produced with enhanced photothermal transformation efficiency and ability to produce reactive oxygen species for synergistic photodynamic photothermal and photodynamic antibacterial performance.The nanoparticles exhibit good antibacterial effects in vitro and satisfactory therapeutic performance on healing MRSA-infected wounds in vivo experiments.RNA-sequencing technique has been used to investigate and reveal that photothermal–photodynamic therapy using the nanoparticles can interfere with metabolic processes such as galactose metabolism in MRSA bacteria,destroy the transport system on the surface of MRSA,and affect quorum sensing to hinder the formation of biofilms to achieve effective antibacterial efficacy.It was demonstrated that this work presents an alternative near-infrared photoactive multimodal nanostructure for antibacterial applications.

Genome-wide analyses of nonsyndromic cleft lip with or without palate identify 20 new risk loci in the Chinese Han population

Orofacial clefts(OFCs),particularly cleft lip with or without cleft palate(CL/P)and cleft palate only(CPO),are among the most common birth defects in humans(Mossey et al.,2009;Dixon et al.,2011).The birth prevalence rate of OFCs in China is reported to be as high as 1.66 per thousand newborns.

Venetoclax and Azacitidine in Chinese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy

Dear Editor,Acute Myeloid Leukemia(AML)patients are often found ineligible for aggressive standard chemotherapy in clinic because of old age and poor conditions.Current evidences suggest that targeted combination therapy might help these patients achieve a higher response rate with acceptable adverse events(AEs).^(1)Venetoclax(VEN),a selective small-molecule BCL2 inhibitor,combined with hypomethylating agent(HMA),such as azacytidine(AZA).

Genome-wide meta-analysis identifies ten new psoriasis susceptibility loci in the Chinese population

Psoriasis is caused by many factors and is characterized by excessive proliferation of the epidermis and erythema with silver scales on the surface of the skin and concomitant with a variety of diseases(Griffiths et al., 2021). Despite the unclear aetiology,increasing evidence has demonstrated that genetic factors play key roles in the pathogenesis of psoriasis.