Bacterial co-infection in COVID-19: a call to stay vigilant.

Co-infection with diverse bacteria is commonly seen in patients infected with the novel coronavirus, SARS-CoV-2. This type of co-infection significantly impacts the occurrence and development of novel coronavirus infection. Bacterial co-pathogens are typically identified in the respiratory system and blood culture, which complicates the diagnosis, treatment, and prognosis of COVID-19, and even exacerbates the severity of disease symptoms and increases mortality rates. However, the status and impact of bacterial co-infections during the COVID-19 pandemic have not been properly studied. Recently, the amount of literature on the co-infection of SARS-CoV-2 and bacteria has gradually increased, enabling a comprehensive discussion on this type of co-infection. In this study, we focus on bacterial infections in the respiratory system and blood of patients with COVID-19 because these infection types significantly affect the severity and mortality of COVID-19. Furthermore, the progression of COVID-19 has markedly elevated the antimicrobial resistance among specific bacteria, such as Klebsiella pneumoniae, in clinical settings including intensive care units (ICUs). Grasping these resistance patterns is pivotal for the optimal utilization and stewardship of antibiotics, including fluoroquinolones. Our study offers insights into these aspects and serves as a fundamental basis for devising effective therapeutic strategies. We primarily sourced our articles from PubMed, ScienceDirect, Scopus, and Google Scholar. We queried these databases using specific search terms related to COVID-19 and its co-infections with bacteria or fungi, and selectively chose relevant articles for inclusion in our review.

An injectable hydrogel based on sodium alginate and gelatin treats bacterial keratitis through multimodal antibacterial strategy.

Bacterial keratitis is among the most prevalent causes of blindness. Currently, the abuse of antibiotics in clinical settings not only lacks bactericidal effects but also readily induces bacterial resistance, making the clinical treatment of bacterial keratitis a significant challenge. In this study, we present an injectable hydrogel (GS-PNH-FF@CuS/MnS) containing self-assembled diphenylalanine dipeptide (FF) and CuS/MnS nanocomposites (CuS/MnS NCs) that destroy bacterial cell walls through a synergistic combination of mild photothermal therapy (PTT), chemodynamic therapy (CDT), ion release chemotherapy, and self-assembled dipeptide contact, thereby eliminating Pseudomonas aeruginosa. Under 808 nm laser irradiation, the bactericidal efficiency of GS-PNH-FF@CuS/MnS hydrogel against P. aeruginosa in vitro reach up to 96.97 %. Furthermore, GS-PNH-FF@CuS/MnS hydrogel is applied topically to kill bacteria, reduce inflammation, and promote wound healing. Hematoxylin-eosin (H&E) staining, Masson staining, immunohistochemistry and immunofluorescence staining are used to evaluate the therapeutic effect on infected rabbit cornea models in vivo. The GS-PNH-FF@CuS/MnS demonstrate good biocompatibility with human corneal epithelial cells and exhibit no obvious eyes side effects. In conclusion, the GS-PNH-FF@CuS/MnS hydrogel in this study provides an effective and safe treatment strategy for bacterial keratitis through a multimodal approach.

Dual-Site Chemosensor for Visualizing •OH-GSH Redox and Tracking Ferroptosis-Inducing Pathways In Vivo.

Oxidative stress, characterized by an imbalance between oxidative and antioxidant processes, results in excessive accumulation of intracellular reactive oxygen species. Among these responses, the regulation of intracellular hydroxyl radicals (•OH) and glutathione (GSH) is vital for physiological processes. Real-time in situ monitoring these two opposing bioactive species and their redox interactions is essential for understanding physiological balance and imbalance. In this study, we developed a dual-site fluorescence chemosensor OG-3, which can independently image both exogenous and endogenous •OH and GSH in separate channels both within cells and in vivo, eliminating issues of spatiotemporal inhomogeneous distribution and cross-interference. With its imaging capabilities of monitoring •OH-GSH redox, OG-3 elucidated two different pathways for ferroptosis induction: (i) inhibition of system xc- to block cystine uptake (extrinsic pathway) and (ii) GPX4 inactivation, leading to the loss of antioxidant defense (intrinsic pathway). Moreover, we assessed the antiferroptotic function and effects of ferroptosis inhibitors by monitoring •OH and GSH fluctuations during ferroptosis. This method provides a reliable platform for identifying potential ferroptosis inhibitors, contributing to our understanding of relevant metabolic and physiological mechanisms. It shows potential for elucidating the regulation of ferroptosis mechanisms and investigating further strategies for therapeutic applications.

Hydroxypropyl methylcellulose reinforced bilayer hydrogel dressings containing L-arginine-modified polyoxometalate nanoclusters to promote healing of chronic diabetic wounds.

Diabetes-related slow healing of wounds is primarily driven by bacterial infections and angiogenesis disorder and presents a substantial hurdle in clinical treatment. To solve the above problems, an advanced multifunctional hydrogel system based on natural polymer was created here to facilitate wound healing in patients with chronic diabetes. The prepared dressing was composed of an outer hydrogel containing polyvinyl alcohol and hydroxypropyl methyl cellulose in dimethyl sulfoxide and water as binary solvents, and an inner hydrogel containing chitosan quaternary ammonium salt, flaxseed gum, and polyvinyl alcohol. Thus, a polysaccharide based bilayer hydrogel (BH) with superior mechanical strength and biocompatibility was created. This bilayer hydrogel could easily bind to dynamic tissue surfaces, thereby generating a protective barrier. Meanwhile, L-arginine-modified polyoxometalate (POM@L-Arg) nanoclusters were loaded in the inner hydrogel. They released NO when stimulated by the peroxide microenvironment of diabetic wounds. NO as a signal molecule regulated vascular tension and promoted cell proliferation and migration. Additionally, because of the synergistic effect of NO and the chitosan quaternary ammonium salt, the hydrogel system exhibited excellent antibacterial performance. The NO released reduced the levels of proinflammatory factors IL-6 and TNF-α in the diabetic wounds, which thus accelerated wound healing. In short, BH + POM@L-Arg is expected to serve as an ideal wound dressing as it exerts a good promotion effect on diabetes-related wound healing.

Preparation of a novel foamed concrete modified with carbon fiber and graphite: Mechanical, electro-magnetic and microstructural characteristics based on X-CT.

In this paper, foam concrete is modified using graphite and carbon fiber as absorbents. The mechanical properties are analyzed in conjunction with hydration products, pore size distribution based on XCT test. Additionally, the resistivity, complex permittivity and complex permeability are tested. The results demonstrate that carbon fiber enhances the proportion of pores with diameters less than 200 µm in foam concrete, thereby significantly enhancing its flexural strength. Furthermore, incorporating graphite helps offset the initial retardation of sulfoaluminate cement hydration induced by carbon fibers, leading to an increase in the average pore size and a reduction in compressive strength. The incorporation of carbon fibers at a concentration of 0.6 wt% achieves the percolation threshold, akin to scenarios with singular fiber incorporation. Exceeding 2 wt% graphite content results in negligible influence on the conductivity. The synergistic integration of graphite and carbon fibers significantly improves the electromagnetic wave absorption performance of the composite. At a thickness of 6 mm, the material exhibits an effective bandwidth where the reflection loss is less than -10 dB, extending up to 2.5 GHz, which constitutes 52.08 % of the tested frequency spectrum.

Sodium hyaluronate hydrogel for wound healing and human health monitoring based on deep eutectic solvent.

Hydrogel dressings traditionally promote wound healing by maintaining moisture and preventing infection rather than by actively stimulating the skin to regulate cell behavior. Electrical stimulation (ES) is known to modulate skin cell behavior and to promote wound healing. This study describes the first multifunctional conductive hydrogel for wound healing and health monitoring based on a deep eutectic solvent (DES). Sodium hyaluronate and polydopamine constituted the hydrogel skeleton, and tea tree oil and Panax notoginseng extract were used as the active ingredients to induce adhesion, promote antioxidant and antibacterial activity, and support biocompatibility of the hydrogel. The inclusion of DES increases the temperature resistance of the hydrogel and improves its environmental adaptability. We used a small, portable coin battery-powered to provide electrical stimulation. Treatment with both the hydrogel and ES resulted in a stronger therapeutic effect than that provided by the commercial DuoDERM dressing. The hydrogel detected movement and strain when applied as a sensor. Overall, this study reports the development of a multifunctional conductive hydrogel dressing based on DES as a wound healing and health monitor.

Double network hydrogel based on curdlan and flaxseed gum with photothermal antibacterial properties for accelerating infectious wound healing.

The healing of infected wounds has always been a clinical challenge. With the increasing threat of drug resistance due to antibiotic overuse, it is imperative to improve antibacterial wound dressings. In this study, we designed a double network (DN) hydrogel via a "one pot method" with antibacterial activity, and natural polysaccharides with the potential to promote skin wound healing were used. That is, a DN hydrogel matrix was formed by the hydrogen bond crosslinking of curdlan and the covalent crosslinking of flaxseed gum under the action of borax. We added ε-polylysine (ε-PL) as a bactericide. Tannic acid/ferric ion (TA/Fe3+) complex was also introduced into the hydrogel network as a photothermal agent to induce photothermal antibacterial properties. The hydrogel had fast self-healing, tissue adhesion, mechanical stability, good cell compatibility and photothermal antibacterial activity. In vitro studies of hydrogel showed its ability to inhibit S. aureus and E. coli. In vivo experiments also demonstrated the significant healing effect of hydrogel when used to treat wounds infected by S. aureus by promoting collagen deposition and accelerating the formation of skin appendage. This work provides a new design for the preparation of safe antibacterial hydrogel wound dressings and demonstrates great potential for promoting wound healing of bacterial infections.

Circular RNA circ_0000741/miR-379-5p/TRIM14 signaling axis promotes HDAC inhibitor (SAHA) tolerance in glioblastoma.

BACKGROUND: Histone deacetylase (HDAC) inhibitor-based therapeutic drug tolerance is a major obstacle to glioblastoma (GBM) treatment. Meanwhile, non-coding RNAs have been reported to be involved in the regulation of HDAC inhibitor (SAHA) tolerance in some human tumors. However, the relationship between circular RNAs (circRNAs) and SAHA tolerance is still unknown. Herein, we explored the role and mechanism of circ_0000741 on SAHA tolerance in GBM. METHODS: Circ_0000741, microRNA-379-5p (miR-379-5p), and tripartite motif-containing 14 (TRIM14) level were detected by real-time quantitative polymerase chain reaction (RT-qPCR). (4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), Colony formation, flow cytometry, and transwell assays were used to detect SAHA tolerance, proliferation, apoptosis, and invasion in SAHA-tolerant GBM cells. Western blot analysis of protein levels of E-cadherin, N-cadherin, and TRIM14. After Starbase2.0 analysis, the binding between miR-379-5p and circ_0000741 or TRIM14 was proved using a dual-luciferase reporter. The role of circ_0000741 on drug tolerance was assessed using a xenograft tumor model in vivo. RESULTS: Circ_0000741 and TRIM14 were upregulated, and miR-379-5p was reduced in SAHA-tolerant GBM cells. Furthermore, circ_0000741 absence reduced SAHA tolerance, suppressed proliferation, invasion, and induced apoptosis in SAHA-tolerant GBM cells. Mechanistically, circ_0000741 might affect TRIM14 content via sponging miR-379-5p. Besides, circ_0000741 silencing enhanced the drug sensitivity of GBM in vivo. CONCLUSION: Circ_0000741 might accelerate SAHA tolerance by regulating the miR-379-5p/TRIM14 axis, which provided a promising therapeutic target for GBM treatment.

Liquid Metal-Doped Conductive Hydrogel for Construction of Multifunctional Sensors.

Interest in wearable and stretchable multifunctional sensors has grown rapidly in recent years. The sensing elements must accurately detect external stimuli to expand their applicability as sensors. However, the sensor's self-healing and adhesion to a target object have been major challenges in developing such practical and versatile devices. In this study, we prepared a hydrogel (LM-SA-PAA) composed of liquid metal (LM), sodium alginate (SA), and poly(acrylic acid) (PAA) with ultrastretchable, excellent self-healing, self-adhesive, and high-sensitivity sensing capabilities that enable the conformal contact between the sensor and skin even during dynamic movements. The excellent self-healing performance of the hydrogel stems from its double cross-linked networks, including physical and chemical cross-linked networks. The physical cross-link formed by the ionic interaction between the carboxyl groups of PAA and gallium ions provide the hydrogel with reversible autonomous repair properties, whereas the covalent bond provides the hydrogel with a stable and strong chemical network. Alginate forms a microgel shell around LM nanoparticles via the coordination of its carboxyl groups with Ga ions. In addition to offering exceptional colloidal stability, the alginate shell has sufficient polar groups, ensuring that the hydrogel adheres to diverse substrates. Based on the efficient electrical pathway provided by the LM, the hydrogel exhibited strain sensitivity and enabled the detection of various human motions and electrocardiographic monitoring. The preparation method is simple and versatile and can be used for the low-cost fabrication of multifunctional sensors, which have broad application prospects in human-machine interface compatibility and medical monitoring.

Verification and Analysis of Filter Paper-Based Intracellular Delivery of Exogenous Substances.

The intracellular delivery of exogenous substances is an essential technical means in the field of biomedical research, including cell therapy and gene editing. Although many delivery technologies and strategies are present, each technique has its own limitations. The delivery cost is usually a major limiting factor for general laboratories. In addition, simplifying the operation process and shortening the delivery time are key challenges. Here, we develop a filter paper-syringe (FPS) delivery method, a new type of cell permeation approach based on filter paper. The cells in a syringe are forced to pass through the filter paper quickly. During this process, external pressure forces the cells to collide and squeeze with the fiber matrix of the filter paper, causing the cells to deform rapidly, thereby enhancing the permeability of the cell membrane and realizing the delivery of exogenous substances. Moreover, the large gap between the fiber networks of filter paper can prevent the cells from bearing high pressure, thus maintaining high cell vitality. Results showed that the slow-speed filter paper used can realize efficient intracellular delivery of various exogenous substances, especially small molecular substances (e.g., 3-5 kDa dextran and siRNA). Meanwhile, we found that the FPS method not only does not require a lengthy operating step compared with the widely used liposomal delivery of siRNA but also that the delivery efficiency is similar. In conclusion, the FPS approach is a simple, easy-to-operate, and fast (about 2 s) delivery method and may be an attractive alternative to membrane destruction-based transfection.

Dual-Site Chemosensor for Monitoring ·OH-Cysteine Redox in Cells and In Vivo.

The reaction between hydroxyl radical (·OH) and cysteine (Cys) plays an important role in the redox balance of living cells. A deeper insight into this intracellular reaction modulation and process is necessary and draws great interest. A highly effective technique consists of the real-time visualization of the two bioactive species and the perception of their respective changes by using a fluorescent probe. In this study, a dual-site chemosensor SPI based on phenothiazine-cyanine was developed, which realized quantitative detection and real-time imaging of ·OH and Cys at their own fluorescence channels (·OH: λex = 485 nm, λem = 608 nm; Cys: λex = 426 nm, λem = 538 nm) without spectral crosstalk. The fluorescent sensor showed excellent anti-interference and selectivity for common biological substances, apart from the successful imaging of exogenous and endogenous ·OH and Cys. We further visualized the redox dynamic reaction and explored the correlation of ·OH and Cys generated by different inhibitors (sulfasalazine and (1S, 3R)-RSL3). Notably, the chemosensor also possesses the capacity to clearly monitor ·OH and Cys in living mice and zebrafish. This study reports on the first chemosensor to investigate the process of intracellular redox modulation and control between ·OH and Cys, which show potential to further explore some metabolic and physiological mechanisms.

Are only-children different? Evidence from a lab-in-the-field experiment of the Chinese one-child policy.

In this paper, we present evidence from a lab-in-the-field experiment of the effects of the Chinese one-child policy on adults in China who were born just before and after the introduction of the policy. We measure risk, uncertainty, and time preferences, as well as subjects' preferences in the social domain, i.e., concerning competitiveness, cooperation, and bargaining. We sampled people from three Chinese provinces born both before and after the introduction of the policy in 1979. We utilize the fact that the one-child policy was introduced at different times and with different degrees of strictness in different provinces. Overall, we find a statistically significant effect only on risk and uncertainty aversion and not on any other preferences in the experiments: Those born after the introduction of the one-child policy are less risk and uncertainty averse. These results hold for various robustness checks and heterogeneity tests. Hence, our results do not confirm the general wisdom and stereotype of only-children in China being "little emperors."

A multifunctional chitosan composite aerogel for PPCPs adsorption.

Pharmaceuticals and personal care products (PPCPs) are gaining attention due to their persistence in the environment. Therefore, the development of novel adsorbents to remove them is strongly anticipated. In this study, an improved dual ice-template assembly method had been used for the preparation of ZIF-67/QGO/SB-CS aerogel through ZIF-67, benzoquinone-modified graphene oxide (QGO), and sulfobetaine-modified chitosan (SB-CS) for the adsorption and removal of PPCPs in water. We reported for the first time that the chitosan composite aerogel has antifouling, bacterial filtration and oil-water separation abilities with excellent PPCPs adsorption performance and reusable, which would be a viable option for long-lasting adsorbents for PPCPs in water.

A highly selective and sensitive CdS fluorescent quantum dot for the simultaneous detection of multiple pesticides.

The abuse of pesticides has introduced a large number of residues in soil and drinking water, which can then enter the food chain and the human body. Monitoring pesticide residues and developing simple and fast detection systems for pesticide residues is urgently needed. In this study, we presented one-pot prepared CdS fluorescent quantum dots (QDs) and explored their sensing application for organic pesticides. The CdS QDs can sensitively and selectively detect three different pesticides, dichlorvos (DDVP), paraquat, and glufosinate-ammonium, through different fluorescence responses. Paraquat can effectively quench the fluorescence of the QDs and DDVP can cause remarkable fluorescent enhancement. Glufosinate-ammonium can induce both 150 nm fluorescent blueshifting and 30-fold fluorescent enhancement. The probe exhibited low detection limits for the three pesticides: 1.44 µM for paraquat, 0.23 mM for DDVP, and 49.8 µM for glufosinate-ammonium. Furthermore, based on the results, we utilized the powerful functions of smartphones to establish a concentration-gray value standard curve through RGB values and gray values to realize the qualitative detection and quantitative analysis of DDVP. It is believed that this work presents a new platform for the simultaneous detection of multiple pesticides using a single QDs probe. The present on-site method using a smartphone is of great potential for water monitoring in rural areas.

hUC-MSCs lyophilized powder loaded polysaccharide ulvan driven functional hydrogel for chronic diabetic wound healing.

In this study, we used the polysaccharide ulvan from the green macroalgae Ulva fenestrata to prepare the hydrogel for chronic diabetic wound healing. A natural polysaccharide-based hydrogel matrix (UC-DPA-Ag hydrogel) was prepared using ulvan dialdehyde, chitosan, dopamine (DPA) and silver nanoparticles (Ag NPs). Human umbilical cord mesenchymal stem cell lyophilized powder (hUC-MSCs) was loaded into the hydrogel to develop a novel chronic diabetic wound healing material (UC-DPA-Ag@hUC-MSCs). The resulting hydrogel features adequate mechanical properties, swelling capability, adhesiveness, antioxidant, antibacterial ability, and promoting cell proliferation and migration. In vivo wound healing in type II diabetic mellitus mouse wound model showed that hUC-MSCs loaded UC-DPA-Ag hydrogel could accelerate wound healing effectively. This advanced hydrogel provides a facile and effective way for diabetic chronic wound management. Furthermore, it offers a new route for the utilizing Ulva as a valuable biomaterial for the global and large-scale production of valued added biomaterials.

Non-biological fluorescent chemosensors for pesticides detection.

The ongoing poisoning of agricultural products has pushed the security problem to become an important issue. Among them, exceeding the standard rate of pesticide residues is the main factor influencing the quality and security of agricultural products. Moreover, the abuse of pesticides has introduced a large amount of residues in soil and drinking water, which will enter the food chain to the human body, leading to neurological disorders and cancer. Therefore, great efforts have been devoted to developing fluorescent sensors for detecting pesticide in a facile, quickly, sensitive, selective, accurate manner, which exhibit greater advantages than some traditional methods. In this review, we mainly focus on summarizing the non-biological fluorescent probes for organic pesticides detection with the detection limit of micromole to nanomole, including organic functional small molecules, calixarenes and pillararenes, metal organic framework systems, and nanomaterials. Meanwhile, we described the different sensing mechanisms for pesticides detection of these mentioned fluorescent sensors, the detection limit of each pesticide, the application in detecting actual samples, as well as their respective advantages and development prospects associated with present non-biological fluorescent sensors.

Preparation of chitosan crosslinked with metal-organic framework (MOF-199)@aminated graphene oxide aerogel for the adsorption of formaldehyde gas and methyl orange.

Chitosan crosslinked with metal-organic framework (MOF-199)@aminated graphene oxide aerogel (MOF-199@AFGO/CS) were prepared to adsorb formaldehyde and methyl orange. The prepared MOF-199@AFGO/CS aerogel was well characterized via SEM, EDX, FT-IR, XRD and XPS to reveal the microstructure and composition. Besides, the mechanical property and the stability of MOF-199@AFGO/CS aerogel were investigated. The results showed that MOF-199@AFGO/CS aerogel had good stability in water, compression resilience and thermostability. The study on the ability to adsorb formaldehyde gas and methyl orange showed that the adsorption capacity of MOF-199@AFGO/CS aerogel was related to the pore size and the surface functional groups of MOF-199@AFGO/CS aerogel. When the pore size is moderate, as the amino group and MOF-199 on the aerogel increased, the adsorption capacity of formaldehyde gas (197.89 mg/g) and methyl orange (412 mg/g) can reach the maximum. Furthermore, the adsorption process at equilibrium followed the Freundlich isotherm model. The kinetic behavior was well fitted by the pseudo-second-order model, indicating chemisorption as the rate-determining step. This work can provide a reliable basis for the adsorbent to remove pollutants in different forms at the same time, and has potential application in simultaneously adsorbing liquid pollutants and gas pollutants.

Preparation of sodium hyaluronate/dopamine/AgNPs hydrogel based on the natural eutetic solvent as an antibaterial wound dressing.

Baesd on previous researches, the natural deep eutectic solvent (DES) has enormous potential to be used in the fabrication of hydrogel wound dressing due to its outstanding properties including cytocompatibility, degradability and solubility. In order to further improve the antibaterial capacity of hydrogel, in the present study sodium hyaluronate (SH) and the natural DES were utilized to develop a novel hydrogel wound dressing by dopamine (DA) coated SH with in situ reduction of silver nanoparticles (DES-DASH@Ag). Furthermore, during the preparation process, we discovered for the first time that the DES can be used to fill the freeze-dried DASH to prepare a hydrogel (DES-DASH), which was promising to utilized in the fabrication of other hydrogels. Besides, the chemical and physical properties as well as wound healing capacity of the DES-DASH@Ag hydrogel were characterized. As a result, the DES-DASH@Ag hydrogel presented good cytocompatibility tested using NIH-3 T3 fibroblast cells, and prominent antibacterial effect against two types of bacteria infecting exposed wound. Furthermore, the hydrogel facilitated regeneration of mouse skin tissue in the wound area. The overall performance of DES-DASH@Ag hydrogel suggested that it could be a promising wound dressing in modern medicine.