The prevalence of hepatitis B virus infection among HIV-infected patients in the Ningxia Hui Autonomous Region, China, November 2002 to July 2023.

We tested HIV-infected people with HBV serological markers of Ningxia. Of 1008 HIV-positive individuals, 70 (6.9 %) tested positive for HBsAg, 570 (56.5 %) tested positive for anti-HBs, and 483 (47.9 %) tested positive for anti-HBc. Of 70 HBV-positive individuals, 13 (18.5 %) tested positive for HBeAg, 31 (44.3 %) tested positive for anti-HBe, 3 (4.2 %) exhibited acute infection.

ARMC10 regulates mitochondrial dynamics and affects mitochondrial function via the Wnt/ß-catenin signalling pathway involved in ischaemic stroke.

Mitochondrial dynamics has emerged as an important target for neuronal protection after cerebral ischaemia/reperfusion. Therefore, the aim of this study was to investigate the mechanism by which ARMC10 regulation of mitochondrial dynamics affects mitochondrial function involved in ischaemic stroke (IS). Mitochondrial morphology was detected by laser scanning confocal microscopy (LSCM), and mitochondrial ultrastructural alterations were detected by electron microscopy. The expression of mitochondrial dynamics-related genes Drp1, Mfn1, Mfn2, Fis1, OPA1 and ARMC10 and downstream target genes c-Myc, CyclinD1 and AXIN2 was detected by RT-qPCR. Western blot was used to detect the protein expression of ß-catenin, GSK-3ß, p-GSK-3ß, Bcl-2 and Bax. DCFH-DA fluorescent probe was to detect the effect of ARMC10 on mitochondrial ROS level, Annexin V-FITC fluorescent probe was to detect the effect of ARMC10 on apoptosis, and ATP assay kit was to detect the effect of ARMC10 on ATP production. Mitochondrial dynamics was dysregulated in clinical IS samples and in the OGD/R cell model, and the relative expression of ARMC10 gene was significantly decreased in IS group (p < 0.05). Knockdown and overexpression of ARMC10 could affect mitochondrial dynamics, mitochondrial function and neuronal apoptosis. Agonist and inhibitor affected mitochondrial function and neuronal apoptosis by targeting Wnt/ß-Catenin signal pathway. In the OGD/R model, ARMC10 affected mitochondrial function and neuronal apoptosis through the mechanism that regulates Wnt/ß-catenin signalling pathway. ARMC10 regulates mitochondrial dynamics and protects mitochondrial function by activating Wnt/ß-catenin signalling pathway, to exert neuroprotective effects.

Mass-Spectrometry-Based Assay at Single-Base Resolution for Simultaneously Detecting m6A and m6Am in RNA.

The methylation modifications of adenosine, especially N6-methyladenosine (m6A) and N6, 2'-odimethyladenosine (m6Am), play vital roles in various biological, physiological, and pathological processes. However, current methods for detecting these modifications at single-base resolution have limitations. Mass spectrometry (MS), a highly accurate and sensitive technique, can be utilized to differentiate between m6A and m6Am by analyzing the molecular weight differences in their fragments during tandem MS analysis. In this study, we present an MS-based method that allows for the simultaneous determination of m6A and m6Am sites in targeted RNA fragments at single-nucleotide resolution. The approach involves the utilization of tandem MS in conjunction with targeted RNA enrichment and enzymatic digestion, eliminating the need for PCR amplification. By employing this strategy, we can accurately identify m6A and m6Am sites in targeted RNA fragments with high confidence. To evaluate the effectiveness of our method, we applied it to detect m6A and m6Am sites in cell and tissue samples. Furthermore, we verified the accuracy of our approach by performing CRISPR/Cas9-mediated knockout of the corresponding methyltransferases. Overall, our MS-based method offers a reliable and precise means for the simultaneous detection of m6A and m6Am modifications in targeted RNA fragments, providing valuable insights into the functional characterization of these modifications in various biological contexts.

Multicomponent Synergistic Antibacterial Hydrogel Based on Gelatin-Oxidized Carboxymethyl Cellulose for Wound Healing of Drug-Resistant Chronic Infection.

Bacterial invasion hinders the healing process of wound, leading to the formation of chronic infected wound; meanwhile, the misuse of antibiotics has resulted in the emergence of numerous drug-resistant bacteria. The application of conventional antimicrobial methods and wound treatment techniques is not appropriate for wound dressings. In this paper, quaternized poly(vinyl alcohol) (QPVA) and pomegranate-like copper uniformly doped polydopamine nanoparticles (PDA@Cu) were introduced into a gelatin-oxidized carboxymethyl cellulose system to form a multicomponent synergistic antibacterial hydrogel (GOQ3P3). Polydopamine improves the biocompatibility and prevents the detachment of Cu nanoparticles. It can achieve synergistic antibacterial effects through quaternary ammonium salt-inorganic nanoparticle photothermal treatment under 808 nm near-infrared (NIR) irradiation. It exhibits highly efficient and rapid bactericidal properties against Escherichia coli, Staphylococcus aureus, and MRSA (methicillin-resistant Staphylococcus aureus) with an antibacterial rate close to 100%. The gel scaffold composed of macromolecules gives the hydrogel excellent mechanical properties, adhesive capabilities, self-healing characteristics, biocompatibility, and pH degradation and promotes cell adhesion and migration. In a full-thickness wound healing model infected with MRSA, GOQ3P3 controls inflammatory responses, accelerates collagen deposition, promotes angiogenesis, and enhances wound closure in the wound healing cascade reaction. This study provides a feasible strategy for constructing dressings targeting chronic infection wounds caused by drug-resistant bacteria.

Antifreezing, Antidrying, and Conductive Hydrogels for Electronic Skin Applications at Ultralow Temperatures.

Although conductive hydrogel-based flexible electronic devices have superb flexibility and high conductivities, they tend to malfunction in dry or frigid areas. Herein, an ultralow-temperature tolerant, antidrying, and conductive composite hydrogel is designed for electronic skin applications on the basis of the synergy of double-cross-linked polymer networks, Hofmeister effect, and electrostatic interaction and fabricated by in situ free radical polymerization of 2-acrylamido-2-methyl-1-propanesulfonic acid and acrylic acid in the presence of poly(vinyl alcohol) and conductive MXene sheets, followed by impregnation with LiCl. Thanks to the synergy of LiCl and the charged polar terminal groups of the synthesized polymers, the composite hydrogel can not only bear an ultralow temperature of -80 °C without freezing but also maintain its original mass. Meanwhile, the resultant hydrogel possesses satisfactory self-regeneration ability benefiting from the moisturizing effect of LiCl. The conductive network of MXene sheets greatly improves the ionic conductivity of the hydrogel at low temperatures, exhibiting an ionic conductivity of 1.4 S m-1 at -80 °C. Furthermore, the electronic skin assembled by the multifunctional hydrogel is efficient in monitoring human motions at -80 °C. The antifreezing and antidrying features along with favorable ionic conductivity, high tensile strength, and outstanding flexibility make the composite hydrogel promising for applications in frigid and dry regions.

Perovskite hydroxide-based laccase mimics with controllable activity for environmental remediation and biosensing.

Constructing relatively inexpensive nanomaterials to simulate the catalytic performance of laccase is of great significance in recent years. Although research on improving laccase-like activity by regulating ligands of copper (amino acids or small organic molecules, etc.) have achieved remarkable success. There are few reports on improving laccase-like activity by adjusting the composition of metal Cu. Here, we used perovskite hydroxide AB(OH)6 as a model to evaluate the relationship between Cu based alloys and their laccase-like activity. We found that when the Cu/Mn alloy ratio of the perovskite hydroxide A point is greater than 1, the laccase-like activity of the binary alloy perovskite hydroxide is higher than that of the corresponding single Cu. Based on the measurements of XPS and ICP-MS, we deduced that the improvements of laccase-like activity mainly attribute to the ratio of Cu+/Cu2+and the content of Cu. Moreover, two types of substrates (toxic pollutants and catechol neurotransmitters) were used to successfully demonstrated such nanozymes' excellent environmental protecting function and biosensing property. This work will provide a novel approach for the construction and application of laccase-like nanozymes in the future.

Tailorable optical properties of polymer nanodots for triple-mode fluorescence detection of nucleic acids.

We present a triple-mode nanosensor platform for nucleic acid detection utilizing fluorescence anisotropy and Förster resonance energy transfer (FRET) strategies. The self-assembled nanoprobes serve as mass amplifiers, nanoquenchers, or nanodonors, exhibiting high FRET efficiencies (64.4-86.5%) and demonstrating excellent detection capabilities in DNA and microRNA analysis.

Dehydration-Toughing Dual-Solvent Gels with Viscoelastic Transition for Infectious Wound Treatment.

The modulus of traditional biomedical hydrogels increases exponentially meditated by dehydration-stiffing mechanism, which leads to the failure of interface matching between hydrogels and soft tissue wounds. It is found in the study that the dual-solvent gels exhibit dehydration-toughening mechanism with the slowly increasing modulus that are always match the soft tissue wounds. Therefore, dual-solvent glycerol hydrogels (GCFen-gly DGHs) are prepared with hydrophobically modified catechol chitosan (hmCSC) and gelatin based on the supramolecular interactions. GCFen-gly DGHs exhibit excellent water retention capacity with a total solvent content exceeding 80%, permanent skin-like modulus within a range of 0.45 to 4.13 kPa, and stable photothermal antibacterial abilities against S, aureus, E. coli, as well as MRSA. Infectious full-thickness rat skin defect model and tissue section analysis indicate that GCFen-gly DGHs are able to accelerate infectious wound healing by alleviating the inflammatory response, promoting granulation tissue growth, re-epithelialization, collagen deposition, and vascular regeneration. As a result, GCFen-gly DGHs is expected to become the next-generation biological gel materials for infectious wound treatment.

Dual-Drug-Loaded Core-Shell Electrospun Nanofiber Dressing for Deep Burns.

The epidermis of a deep burn wound is entirely absent and the dermal tissue sustains significant damage, accompanied by a substantial amount of tissue exudate. Due to the excessively humid environment, the formation of a scab on the wound becomes challenging, leaving it highly vulnerable to external bacterial invasion. In this work, a core-shell dual-drug-loaded nanofiber dressing was prepared by electrospinning technology for the synergistic treatment of a deep burn. The shell layer consists of polycaprolactone and chitosan encapsulating asiaticoside, with the core layer comprising the clathrate of 2-hydroxypropyl-ß-cyclodextrin and curcumin. Upon application to the wound, the dual-drug-loaded nanofiber dressing exhibited rapid release of asiaticoside, stimulating collagen deposition and promoting tissue repair. The core-shell structure and clathrate configuration ensured sustained release of curcumin, providing antibacterial and anti-inflammatory functions for the wound. The mechanical strength, broad-spectrum antibacterial ability, cell proliferation, and adhesion ability of the nanofiber dressing showed its potential as a medical dressing. This dressing also exhibited excellent wound healing promoting effects in the SD rat burn model. This paper provides a strategy for burn wound healing.

Target immobilization on glass microfiber membranes as a label-free strategy for hit identification.

The discovery of novel chemical entities targeting G protein-coupled receptors (GPCRs) is usually guided by their receptor affinity. However, traditional affinity assay methods and hit identification procedures are usually laborious and expensive. In this work, the type-2 vasopressin receptor (V2R) was chosen as a prototypical GPCR. Membrane fragments from cells highly expressing SNAP-V2R were immobilized on the surface of a glass microfiber (GMF) coated with O6-benzylguanine (BG). This was achieved by transferring the benzyl group of BG to the active site of the SNAP-tag through a nucleophilic substitution reaction. As a result, a biofilm called SNAP-V2R@GMF-BG was produced that showed good specificity and stability. The adsorption ratio for each V2R ligand treated with SNAP-V2R@GMF-BG was determined by HPLC and exhibited a good linear correlation with the Ki value determined by displacement assays. Furthermore, a Ki prediction assay was performed by comparing the data with that generated by a homogeneous time-resolved fluorescence (HTRF) assay. SNAP-V2R@GMF-BG was also used to screen hit compounds from natural products. After SNAP-V2R@GMF-BG was incubated with the total extract, the ligand that binds to V2R could be separated and subjected to LC‒MS analysis for identification. Baicalein was screened from Clerodendranthus spicatus and verified as a potential V2R antagonist. This V2R-immobilized GMF platform can help determine the affinity of V2R-binding hit compounds and screen the compounds efficiently and accurately.

A laser free self-luminous nanosystem for photodynamic therapy of cervical cancer cells.

Photodynamic therapy is a tumor treatment strategy. However, most of the photodynamic therapies rely on laser irradiation triggering, which limits their application in deep tissues. This study designed a self-luminescent nano system, hybrid protein oxygen nanocarrier coated graphene quantum dots (GQDs@HPOC) and mesoporous silica nanoparticles coated Luminol (L@MSNs), which self-assembled into GQDs@HPOC/L@MSNs without laser irradiation. The system utilized the weak acidic environment of tumors to trigger the release of Luminol and the chemiluminescence was catalyzed by HPOC. Next CRET occurred between Luminol and GQDs, producing 1O2, which could generate photodynamic damage to cervical cancer cells without the need for external laser irradiation. The system achieved the peak uptake in primary cervical cancer cells in 3 h, and had good biosafety before self-assembly. The system could significantly kill cells at a concentration of 16 µg/ml. The system will be further applied in in vivo experiments to investigate its therapeutic ability, providing a new strategy for the clinical treatment of cervical cancer.

A dual-ratio fluorescent probe with a single excitation triple-signal to synchronously detect PTK7 and miRNA-21 for breast cancer early diagnosis.

The measurement of tumor biomarker levels is of great significance for early diagnosis of breast cancer. The combination diagnosis of multiple tumor biomarkers will significantly improve the accuracy of early diagnosis. Here, we successfully developed a dual-ratio fluorescent sensing platform for the detection of breast cancer biomarkers (PTK7, miRNA-21) using single excitation triple-signal detection. Introducing three types of fluorescence nanomaterials with narrow emission peaks and long Stokes shift as signal markers, the three peaks (430 nm, 530 nm and 640 nm) of which do not interfere with each other in fluorescence spectra under a single excitation (360 nm). The sensing platform linked aptamer (apt) modified green fluorescence quantum dots (gQDs-apt1) and aptamer modified red fluorescence quantum dots (rQDs-apt2) to Fe3O4-cDNA1 and Fe3O4-cDNA2, respectively, via base complementary pairing with aptamer molecules. When PTK7/miRNA-21 is present in the system, gQDs-apt1/rQDs-apt2 bound to the Fe3O4 MNPs surface will be released to recover fluorescence. Upon DNase I digestion of free apt1 and apt2, the target molecules will be released to bind to gQDs-apt1/rQDs-apt2 for signal amplification. After magnetic separation, PTK7 and miRNA-21 can be quantified using the fluorescence intensity ratio of gQDs with bCDs and rQDs with bCDs at a single excitation of 360 nm wavelength. This method has high sensitivity, good selectivity, and can quantify both PTK7 and miRNA-21 simultaneously with an LOD of 0.426 ng mL-1 and 0.072 nM, respectively. Additionally, the sensing platform was used for serum detection of health man and breast cancer patients with satisfactory results.

Tumor-Associated Macrophages Regulating a Polymer Nanoplatform for Synergistic Treatment of Breast Tumors.

Tumor-associated macrophages (TAMs) play a critical role in tumor progression and metastasis. Modulation of TAM polarization is one of the most effective strategies to change the immunosuppressive tumor microenvironment (TME). In this study, organic polymer nanoparticles (CPHT) were prepared using hyaluronic acid (HA)-conjugated disulfide-bonded polyethylene imide (PEIS) as a carrier through a self-assembly strategy. These nanoparticles were modified by transferrin (Tf) and loaded with chlorin e6 (Ce6). The results showed that CPHT had good dispersion with a particle size of about 30 nm. CPHT gradually disintegrated under the exposure with a high concentration of glutathione (GSH) in tumor cells, proving the possibility for the controlled release of Ce6 and photodynamic therapy. An in vitro test showed that the uptake of CPHT in tumor cells was mediated by both HA and Tf, indicating the active tumor-targeting capacity of CPHT. CPHT significantly downregulated the ratio of CD206/CD86 and triggered the upregulation of immune factors such as TNF-α and iNOS, suggesting the repolarization of TAMs. We also found that CPHT effectively induced ferroptosis in tumor cells through lipid peroxide accumulation, GSH depletion, and downregulation of lipid peroxidase (GPX4) expression. Animal experiments confirmed that CPHT not only effectively inhibited the growth of tumors in situ but also significantly decelerated the growth of the distal tumor. Elevated levels of CD86 and IFN-γ and decreased expression of CD206 were observed at the tumor sites post CPHT treatment. These results confirmed the value of CPHT as a multifunctional nanoplatform that can tune the TME and provide new hope for tumor treatment.

Adaptive and Adjustable MXene/Reduced Graphene Oxide Hybrid Aerogel Composites Integrated with Phase-Change Material and Thermochromic Coating for Synchronous Visible/Infrared Camouflages.

Although single-function camouflage under infrared/visible bands has made great advances, it is still difficult for camouflage materials to cope with the synergy detection spanning both visible and infrared spectra and adapt to complex and variable scenarios. Herein, a trilayer composite integrating thermal insulation, heat absorption, solar/electro-thermal conversions, and thermochromism is fabricated for visible and infrared dual camouflages by combining anisotropic MXene/reduced graphene oxide hybrid aerogel with the n-octadecane phase change material in its bottom and a thermochromic coating on its upper surface. Benefiting from the synergetic heat-transfer suppression derived from the thermal insulation of the porous aerogel layer and the heat absorption of the n-octadecane phase-change layer, the composite can serve as a cloak to hide the target signatures from the infrared images of its ambient surroundings during the day in the jungle and at night in all scenes and can assist the target in escaping visual surveillance by virtue of its green appearance. For desert scenarios, the composite can spontaneously increase its surface temperature via its solar-thermal energy conversion, merging infrared images of the targets into the high-temperature surroundings; meanwhile, it can vary the surface color from the original green to yellow, enabling the target to visually disappear from ambient sands and hills. This work provides a promising strategy for designing adaptive and adjustable integrated camouflage materials to counter multiband surveillance in complicated environments.

A fluorescent probe for protein tyrosine kinase 7 detection in serum and cell imaging.

Tyrosine protein kinase 7 (PTK7) is overexpressed in breast cancer, which is considered as a cancer marker for breast cancer diagnosis. Therefore, a simple fluorescent probe for PTK7 detection and cell imaging was developed. In the developed probe, Fe3O4 magnetic nanoparticles were used as the fluorescent separator, and the fluorescence of carbon dots were used as the detection signal. The probe was worked by control the configurations of the aptamer of PTK7, the aptamer would be open chains by recognition of PTK7, which bond with carbon dots and show fluorescent signal. Based on the remarkably high affinity and selectivity of aptamer for PTK7, the excellent fluorescence property of carbon dots and the outstanding magnetism of Fe3O4 magnetic nanoparticles, the developed probe showed satisfied results for PTK7 detection in serum and MCF-7 cell imaging. The probe detected PTK7 in the range of 0.2-200 ng mL-1 with a detection limit of 0.0347 ng mL-1, and successfully imaged the cancer cell expressed PTK7. The results indicate that the nano-fluorescent probe has great potential for clinical applications.

A carbon monoxide releasing metal organic framework nanoplatform for synergistic treatment of triple-negative breast tumors.

BACKGROUND: Carbon monoxide (CO) is an important signaling molecule participating in multiple biological functions. Previous studies have confirmed the valuable roles of CO in cancer therapies. If the CO concentration and distribution can be controlled in tumors, new cancer therapeutic strategy may be developed to benefit the patient survival. RESULTS: In this study, a UiO-67 type metal-organic framework (MOF) nanoplatform was produced with cobalt and ruthenium ions incorporated into its structure (Co/Ru-UiO-67). Co/Ru-UiO-67 had a size range of 70-90 nm and maintained the porous structure, with cobalt and ruthenium distributed uniformly inside. Co/Ru-UiO-67 was able to catalyze carbon dioxide into CO upon light irradiation in an efficient manner with a catalysis speed of 5.6 nmol/min per 1 mg Co/Ru-UiO-67. Due to abnormal metabolic properties of tumor cells, tumor microenvironment usually contains abundant amount of CO2. Co/Ru-UiO-67 can transform tumor CO2 into CO at both cellular level and living tissues, which consequently interacts with relevant signaling pathways (e.g. Notch-1, MMPs etc.) to adjust tumor microenvironment. With proper PEGylation (pyrene-polyacrylic acid-polyethylene glycol, Py-PAA-PEG) and attachment of a tumor-homing peptide (F3), functionalized Co/Ru-UiO-67 could accumulate strongly in triple-negative MDA-MB-231 breast tumors, witnessed by positron emission tomography (PET) imaging after the addition of radioactive zirconium-89 (89Zr) into Co-UiO-67. When applied in vivo, Co/Ru-UiO-67 could alter the local hypoxic condition of MDA-MB-231 tumors, and work synergistically with tirapazamine (TPZ). CONCLUSION: This nanoscale UiO-67 MOF platform can further our understanding of CO functions while produce CO in a controllable manner during cancer therapeutic administration.

Decrease of MtDNA copy number affects mitochondrial function and involves in the pathological consequences of ischaemic stroke.

The mtDNA copy number can affect the function of mitochondria and play an important role in the development of diseases. However, there are few studies on the mechanism of mtDNA copy number variation and its effects in IS. The specific mechanism of mtDNA copy number variation is still unclear. In this study, mtDNA copy number of 101 IS patients and 101 normal controls were detected by qRT-PCR, the effect of D-loop variation on mtDNA copy number of IS patients was explored. Then, a TFAM gene KD-OE PC12 cell model was constructed to explore the effect of mtDNA copy number variation on mitochondrial function. The results showed that the mtDNA copy number level of the IS group was significantly lower than that of the normal control group (p < 0.05). The relative expression of TFAM gene mRNA in the cells of the OGD/R treatment group was significantly lower than that of the control group (p < 0.05). In addition, after TFAM gene knockdown and over-expression plasmids were transfected into HEK 293T cells, mtDNA copy number and ATP production level of Sh-TFAM transfection group was significantly decreased (p < 0.05), while mtDNA copy number and ATP production level of OE-TFAM transfected group were significantly higher than that of blank control group and OE-ctrl negative control group (p < 0.01). Our study demonstrated that mitochondrial D-loop mutation and TFAM gene dysfunction can cause the decrease of mtDNA copy number, thus affecting the mitochondrial metabolism and function of nerve cells, participating in the pathological damage mechanism of IS.

Super-Hygroscopic Calcium Chloride/Graphene Oxide/Poly(N-isopropylacrylamide) Gels for Spontaneous Harvesting of Atmospheric Water and Solar-Driven Water Release.

Although atmospheric water harvesting is a promising approach for extracting clean water in water deficient areas, most atmospheric water collectors require additional energy for releasing the water absorbed. It is still challenging to improve both moisture absorption capacity and desorption efficiency of moisture water collectors. Inspired by clean solar energy and the large humidity difference between day and night, super-hygroscopic calcium chloride (CaCl2)/graphene oxide (GO)/poly(N-isopropylacrylamide) (PNIPAM) gels are designed for spontaneous collection of atmospheric water in a wide range of relative humidity (RH) followed by solar-driven release of the water absorbed. An optimal CaCl2/GO/PNIPAM hygroscopic gel possesses a hierarchical porous structure with directional water transport channels, facilitating water capture and release, thus exhibiting a high moisture absorption capacity of up to 3.6 g g-1 at an RH of 90%. Driven by simulated sunlight, the solar-thermal energy conversion effect of the GO component triggers a unique hydrophilic-hydrophobic conformational transition and shrinkage of the PNIPAM for efficient release of the water absorbed. The integration of the spontaneous harvesting of atmospheric water and the solar-driven water release makes the super-hygroscopic gels promising for efficiently utilizing atmospheric water for special applications where water is desperately necessary but unavailable.

Smart Hydrogel Sensors with Antifreezing, Antifouling Properties for Wound Healing.

Flexible electronic devices with biological therapeutic and sensing properties are one of the current research directions. Here, a multifunctional hydrogel for stress sensing and wound healing was prepared by a simple one-pot method and a solution replacement method. Among them, zwitterionic polymers promote wound healing by promoting the polarization of M2 macrophages, collagen deposition, and blood vessel formation. Glycerin can significantly improve the resilience and frost resistance of the hydrogel, ensuring that a sensor made using the hydrogel can work normally in a cold environment. In addition, zwitterionic polymers are highly biocompatible, providing excellent antibacterial adhesion to aid the wound healing process, and good electrical conductivity enhances sensing sensitivity and stability. Based on these properties, multifunctional hydrogels could detect human vital activities while promoting wound healing, providing new ideas for the fields of diagnosis and wound dressing.