Black phosphorus nanosheets activate tumor immunity of glioblastoma by modulating the expression of the immunosuppressive molecule PD-L1.

The tumor microenvironment in glioblastoma (GBM) is characterized by a pronounced immunosuppressive state, which significantly hampers tumor treatment and contributes to treatment resistance. While our previous research established that black phosphorus nanosheets (BPNS) inhibited glioblastoma cell migration and invasion, the impact of BPNS on the anti-tumor-associated immune mechanism remains unexplored. This study firstly investigated whether BPNS could modulate the tumor microenvironment through immunotherapy and elucidated the underlying mechanisms.

Discovery of a novel CDK4/6 and HDAC dual-targeting agent for the treatment of hepatocellular carcinoma.

The down-regulation of p21 after long-term CDK4/6 inhibition represents a key mechanism causing resistance to CDK4/6 inhibitors in some tumor cells, while the HDAC inhibitor could upregulate the level of p21. Herein, a series of novel CDK4/6 and HDAC dual-targeting inhibitors based on the moiety of palbociclib were designed and synthesized. Among them, compound N14 potently inhibited CDK4/6 and HDAC1/6 at nanomolar levels and induced cell apoptosis and G/G phase arrest through HDAC-p21-CDK signaling pathway in HuH-7 cell line.

An MSRE-Assisted Glycerol-Enhanced RPA-CRISPR/Cas12a Method for Methylation Detection.

Background: Nasopharyngeal carcinoma (NPC) is a malignant tumor with high prevalence in southern China. Aberrant DNA methylation, as a hallmark of cancer, is extensively present in NPC, the detection of which facilitates early diagnosis and prognostic improvement of NPC. Conventional methylation detection methods relying on bisulfite conversion have limitations such as time-consuming, complex processes and sample degradation; thus, a more rapid and efficient method is needed.

As air relative humidity increases, infectivity of SARS-CoV-2 decreases within water droplets.

Water droplets containing the SARS-CoV-2 virus, responsible for coronavirus 2019 transmission, were introduced into a controlled-temperature and -humidity chamber. The SARS-CoV-2 virus with green fluorescent protein tag in droplets was used to infect Caco-2 cells, with viability assessed through flow cytometry and microscopic counting. Whereas temperature fluctuations within typical indoor ranges (20°C-30°C) had minimal impact, we observed a notable decrease in infection rate as the surrounding air's relative humidity increased.

Exploring distinct modes of inter-spike cross-linking for enhanced neutralization by SARS-CoV-2 antibodies.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its Omicron subvariants drastically amplifies transmissibility, infectivity, and immune escape, mainly due to their resistance to most neutralizing antibodies. Thus, exploring the mechanisms underlying antibody evasion is crucial. Although the full-length native form of antibody, immunoglobulin G (IgG), offers valuable insights into the neutralization, structural investigations primarily focus on the fragment of antigen-binding (Fab).

Catalytic Intermolecular Asymmetric [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes: Practical Synthesis of Enantioenriched Highly Substituted Bicyclo[2.1.1]hexanes.

The high percentage of sp-hybridized carbons and the presence of chiral carbon centers could contribute to increased molecular complexity, enhancing the likelihood of clinical success of drug candidates. Three-dimensional (3D) bridged motifs have recently garnered significant interest in medicinal chemistry. Bicyclo[2.

Super broad and protective nanobodies against Sarbecoviruses including SARS-CoV-1 and the divergent SARS-CoV-2 subvariant KP.3.1.1.

The ongoing evolution and immune escape of SARS-CoV-2, alongside the potential threat of SARS-CoV-1 and other sarbecoviruses, underscore the urgent need for effective strategies against their infection and transmission. This study highlights the discovery of nanobodies from immunized alpacas, which demonstrate exceptionally broad and potent neutralizing capabilities against the recently emerged and more divergent SARS-CoV-2 Omicron subvariants including JD.1.

Ultrasound-Responsive Lipid Nanoplatform with Nitric Oxide and Carbon Monoxide Release for Cancer Sono-Gaso-Therapy.

Local gas therapy is emerging as a potential cancer treatment approach due to its specificity as gas-containing molecules can be packed into a nanodelivery system to release the corresponding gaseous molecules around the tumor site upon a suitable stimulus. Single-gas therapy has been reported, while synergistic dual-gas therapy has rarely been reported. Herein, we report a dual-gas-containing nanoplatform for synergistic cancer gasotherapy upon ultrasound irradiation.

Fostering rehydration and facilitating bioactive release through cellulose-assisted leaf surface treatment.

Glyphosate is a widely used herbicide in weed control and crop protection. However, its low bioavailability on leaf surfaces of weeds led to excessive use of glyphosate, inducing herbicide-resistant development and major sustainable agricultural and environmental concerns. This study addresses these challenges by developing cellulose-assisted glyphosate formulations using superior rehydration and sustainable release capability of nanocelluloses.

SubCELL: the landscape of subcellular compartment-specific molecular interactions.

The subcellular compartment-specific molecular interactions (SCSIs) are the building blocks for most molecular functions, biological processes and disease pathogeneses. Extensive experiments have therefore been conducted to accumulate the valuable information of SCSIs, but none of the available databases has been constructed to describe those data. In this study, a novel knowledge base SubCELL is thus introduced to depict the landscape of SCSIs among DNAs/RNAs/proteins.

Cell Membrane-Coated Nanoparticles for Dental, Oral, and Craniofacial Diseases.

Dental, oral, and craniofacial diseases can substantially impact the quality of human life, thereby posing a serious public health concern. Although conventional therapies such as surgery have solved these problems largely, the prognosis of patients is not always satisfactory. Cell membrane-coated nanoparticles (CMCNPs) carry nanodrugs with the help of natural cell membranes, therefore utilizing their remarkable ability to interface and interact with their surrounding environment.

Design and Synthesis of c-Met and HDAC Dual Inhibitors for the Treatment of Breast Cancer.

In recent years, it has been proposed that c-mesenchymal-to-epithelial transition factor (c-Met) and histone deacetylase (HDAC) dual inhibition is a promising cancer treatment strategy. Herein, a series of c-Met/HDAC dual inhibitors were designed and synthesized given their synergistic anticancer effect in breast cancer cells. Compound exhibited excellent inhibitory activity against c-Met (IC = 28.

An immunotherapeutic hydrogel booster inhibits tumor recurrence and promotes wound healing for postoperative management of melanoma.

Low tumor immunogenicity, immunosuppressive tumor microenvironment, and bacterial infections have emerged as significant challenges in postsurgical immunotherapy and skin regeneration for preventing melanoma recurrence. Herein, an immunotherapeutic hydrogel booster (GelMA-CJCNPs) was developed to prevent postoperative tumor recurrence and promote wound healing by incorporating ternary carrier-free nanoparticles (CJCNPs) containing chlorine e6 (Ce6), a BRD4 inhibitor (JQ1), and a glutaminase inhibitor (C968) into methacrylic anhydride-modified gelatin (GelMA) dressings. GelMA-CJCNPs reduced glutathione production by inhibiting glutamine metabolism, thereby preventing the destruction of reactive oxygen species generated by photodynamic therapy, which could amplify oxidative stress to induce severe cell death and enhance immunogenic cell death.

An IGHG1 variant exhibits polarized prevalence and confers enhanced IgG1 antibody responses against life-threatening organisms.

Evolutionary pressures sculpt population genetics, whereas immune adaptation fortifies humans against life-threatening organisms. How the evolution of selective genetic variation in adaptive immune receptors orchestrates the adaptation of human populations to contextual perturbations remains elusive. Here, we show that the G396R coding variant within the human immunoglobulin G1 (IgG1) heavy chain presents a concentrated prevalence in Southeast Asian populations.

DNA-Engineered Degradable Invisibility Cloaking for Tumor-Targeting Nanoparticles.

Nanoparticle (NP) delivery systems have been actively exploited for cancer therapy and vaccine development. Nevertheless, the major obstacle to targeted delivery lies in the substantial liver sequestration of NPs. Here we report a DNA-engineered approach to circumvent liver phagocytosis for enhanced tumor-targeted delivery of nanoagents in vivo.

Raman spectroscopic deep learning with signal aggregated representations for enhanced cell phenotype and signature identification.

Feature representation is critical for data learning, particularly in learning spectroscopic data. Machine learning (ML) and deep learning (DL) models learn Raman spectra for rapid, nondestructive, and label-free cell phenotype identification, which facilitate diagnostic, therapeutic, forensic, and microbiological applications. But these are challenged by high-dimensional, unordered, and low-sample spectroscopic data.

Engineering Bacteria and Their Derivatives for Cancer Immunotherapy.

Leveraging bacteria for cancer immunotherapy has gradually attracted wide attention since the discovery of "Cloey's toxin." However, one of the persistent challenges for bacteria-based therapy is striking a balance between safety and immunogenicity. Genetically engineered bacteria with virulence factors removed could further enhance antitumor ability by integrating genetic elements.

Framework nucleic acid-based nanoparticles enhance temozolomide sensitivity in glioblastoma.

O-methylguanine DNA methyltransferase (MGMT) is a crucial determinant of temozolomide (TMZ) sensitivity in patients with glioblastoma (GBM). The therapeutic potential of small interfering RNA (siRNA) targeting MGMT to enhance TMZ sensitivity has been hampered by serum nuclease degradation, off-target effects, poor accumulation at tumor sites, and low circulation in blood stream. In this study, we developed a framework nucleic acid-based nanoparticles (FNN), which is constructed from a six-helix DNA bundle, to encapsulate and protect siMGMT for improving TMZ sensitivity in GBM treatment.

"Two-birds-one-stone" oral nanotherapeutic designed to target intestinal integrins and regulate redox homeostasis for UC treatment.

Designing highly efficient orally administrated nanotherapeutics with specific inflammatory site-targeting functions in the gastrointestinal tract for ulcerative colitis (UC) management is a noteworthy challenge. Here, we focused on exploring a specific targeting oral nanotherapy, serving as "one stone," for the directed localization of inflammation and the regulation of redox homeostasis, thereby achieving effects against "two birds" for UC treatment. Our designed nanotherapeutic agent OPNs@LMWH (oxidation-sensitive ε-polylysine nanoparticles at low-molecular weight heparin) exhibited specific active targeting effects and therapeutic efficacy simultaneously.

Lycium ruthenicum water extract preserves retinal ganglion cells in chronic ocular hypertension mouse models.

Murray (LR) known as "black goji berry" or "black wolfberry", is widely utilized in chinese herbal medicine. LR fruit showed its antioxidant and/or anti-inflammation activity in treating cardiac injury, experimental colitis, nonalcoholic fatty liver disease, fatigue, and aging. Glaucoma is the leading cause of irreversible blindness.

Phosphoribosylpyrophosphate synthetase as a metabolic valve advances Methylobacterium/Methylorubrum phyllosphere colonization and plant growth.

The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive.

Enzyme-free method for preparation of sturgeon extracts with antioxidant, hepatoprotective and immune-enhancing functions.

Sturgeon has a long lifespan and slow evolutionary rate due to their powerful endogenous antioxidant system. This work aimed to assess the in vitro and in vivo antioxidant activity of sturgeon extracts from both muscle and roe. The extraction process without enzyme hydrolysis is not only simple, but also can produce extracts with better free radicals scavenging abilities than enzymatic hydrolysates in both cellular and in vivo experiments.