A General Molecular Structural Design for Highly Efficient Photopyroptosis that can be Activated within 10 s Irradiation.

Photopyroptosis is an emerging research branch of photodynamic therapy (PDT), whereas there remains a lack of molecular structural principles to fabricate photosensitizers for triggering a highly efficient pyroptosis. Herein, a general and rational structural design principle to implement this hypothesis, is proposed. The principle relies on the clamping of cationic moieties (e.g., pyridinium, imidazolium) onto one photosensitive core to facilitate a considerable mitochondrial targeting (both of the inner and the outer membranes) of the molecules, thus maximizing the photogenerated reactive oxygen species (ROS) at the specific site to trigger the gasdermin E-mediated pyroptosis. Through this design, the pyroptotic trigger can be achieved in a minimum of 10 s of irradiation with a substantially low light dosage (0.4 J cm⁻2), compared to relevant work reported (up to 60 J cm⁻2). Moreover, immunotherapy with high tumor inhibition efficiency is realized by applying the synthetic molecules alone. This structural paradigm is valuable for deepening the understanding of PDT (especially the mitochondrial-targeted PDT) from the perspective of pyroptosis, toward the future development of the state-of-the-art form of PDT.

Adipose-derived stem cells derived decellularized extracellular matrix enabled skin regeneration and remodeling.

The tissues or organs derived decellularized extracellular matrix carry immunogenicity and the risk of pathogen transmission, resulting in limited therapeutic effects. The cell derived dECM cultured in vitro can address these potential risks, but its impact on wound remodeling is still unclear. This study aimed to explore the role of decellularized extracellular matrix (dECM) extracted from adipose derived stem cells (ADSCs) in skin regeneration. Methods: ADSCs were extracted from human adipose tissue. Then we cultivated adipose-derived stem cell cells and decellularized ADSC-dECM for freeze-drying. Western blot (WB), enzyme-linked immunosorbent assay (ELISA) and mass spectrometry (MS) were conducted to analyzed the main protein components in ADSC-dECM. The cell counting assay (CCK-8) and scratch assay were used to explore the effects of different concentrations of ADSC-dECM on the proliferation and migration of human keratinocytes cells (HaCaT), human umbilical vein endothelia cells (HUVEC) and human fibroblasts (HFB), respectively. Moreover, we designed a novel ADSC-dECM-CMC patch which used carboxymethylcellulose (CMC) to load with ADSC-dECM; and we further investigated its effect on a mouse full thickness skin wound model. Results: ADSC-dECM was obtained after decellularization of in vitro cultured human ADSCs. Western blot, ELISA and mass spectrometry results showed that ADSC-dECM contained various bioactive molecules, including collagen, elastin, laminin, and various growth factors. CCK-8 and scratch assay showed that ADSC-dECM treatment could significantly promote the proliferation and migration of HaCaT, human umbilical vein endothelia cells, and human fibroblasts, respectively. To evaluate the therapeutic effect on wound healing in vivo, we developed a novel ADSC-dECM-CMC patch and transplanted it into a mouse full-thickness skin wound model. And we found that ADSC-dECM-CMC patch treatment significantly accelerated the wound closure with time. Further histology and immunohistochemistry indicated that ADSC-dECM-CMC patch could promote tissue regeneration, as confirmed via enhanced angiogenesis and high cell proliferative activity. Conclusion: In this study, we developed a novel ADSC-dECM-CMC patch containing multiple bioactive molecules and exhibiting good biocompatibility for skin reconstruction and regeneration. This patch provides a new approach for the use of adipose stem cells in skin tissue engineering.

Linking preoperative and early intensive care unit data for prolonged intubation prediction.

Objectives: Prolonged intubation (PI) is a frequently encountered severe complication among patients following cardiac surgery (CS). Solely concentrating on preoperative data, devoid of sufficient consideration for the ongoing impact of surgical, anesthetic, and cardiopulmonary bypass procedures on subsequent respiratory system function, could potentially compromise the predictive accuracy of disease prognosis. In response to this challenge, we formulated and externally validated an intelligible prediction model tailored for CS patients, leveraging both preoperative information and early intensive care unit (ICU) data to facilitate early prophylaxis for PI. Methods: We conducted a retrospective cohort study, analyzing adult patients who underwent CS and utilizing data from two publicly available ICU databases, namely, the Medical Information Mart for Intensive Care and the eICU Collaborative Research Database. PI was defined as necessitating intubation for over 24 h. The predictive model was constructed using multivariable logistic regression. External validation of the model's predictive performance was conducted, and the findings were elucidated through visualization techniques. Results: The incidence rates of PI in the training, testing, and external validation cohorts were 11.8%, 12.1%, and 17.5%, respectively. We identified 11 predictive factors associated with PI following CS: plateau pressure [odds ratio (OR), 1.133; 95% confidence interval (CI), 1.111-1.157], lactate level (OR, 1.131; 95% CI, 1.067-1.2), Charlson Comorbidity Index (OR, 1.166; 95% CI, 1.115-1.219), Sequential Organ Failure Assessment score (OR, 1.096; 95% CI, 1.061-1.132), central venous pressure (OR, 1.052; 95% CI, 1.033-1.073), anion gap (OR, 1.075; 95% CI, 1.043-1.107), positive end-expiratory pressure (OR, 1.087; 95% CI, 1.047-1.129), vasopressor usage (OR, 1.521; 95% CI, 1.23-1.879), Visual Analog Scale score (OR, 0.928; 95% CI, 0.893-0.964), pH value (OR, 0.757; 95% CI, 0.629-0.913), and blood urea nitrogen level (OR, 1.011; 95% CI, 1.003-1.02). The model exhibited an area under the receiver operating characteristic curve (AUROC) of 0.853 (95% CI, 0.840-0.865) in the training cohort, 0.867 (95% CI, 0.853-0.882) in the testing cohort, and 0.704 (95% CI, 0.679-0.727) in the external validation cohort. Conclusions: Through multicenter internal and external validation, our model, which integrates early ICU data and preoperative information, exhibited outstanding discriminative capability. This integration allows for the accurate assessment of PI risk in the initial phases following CS, facilitating timely interventions to mitigate adverse outcomes.

Conditional survival analysis and dynamic prediction of long-term survival in Merkel cell carcinoma patients.

Background: Merkel cell carcinoma (MCC) is a rare type of invasive neuroendocrine skin malignancy with high mortality. However, with years of follow-up, what is the actual survival rate and how can we continually assess an individual's prognosis? The purpose of this study was to estimate conditional survival (CS) for MCC patients and establish a novel CS-based nomogram model. Methods: This study collected MCC patients from the Surveillance, Epidemiology, and End Results (SEER) database and divided these patients into training and validation groups at the ratio of 7:3. CS refers to the probability of survival for a specific timeframe (y years), based on the patient's survival after the initial diagnosis (x years). Then, we attempted to describe the CS pattern of MCCs. The Least absolute shrinkage and selection operator (LASSO) regression was employed to screen predictive factors. The Multivariate Cox regression analysis was applied to demonstrate these predictors' effect on overall survival and establish a novel CS-based nomogram. Results: A total of 3,843 MCC patients were extracted from the SEER database. Analysis of the CS revealed that the 7-year survival rate of MCC patients progressively increased with each subsequent year of survival. The rates progressed from an initial 41-50%, 61, 70, 78, 85%, and finally to 93%. And the improvement of survival rate was nonlinear. The LASSO regression identified five predictors including patient age, sex, AJCC stage, surgery and radiotherapy as predictors for CS-nomogram development. And this novel survival prediction model was successfully validated with good predictive performance. Conclusion: CS of MCC patients was dynamic and increased with time since the initial diagnosis. Our newly established CS-based nomogram can provide a dynamic estimate of survival, which has implications for follow-up guidelines and survivorship planning, enabling clinicians to guide treatment for these patients better.

Enhancement of medium-chain fatty acids production from sludge anaerobic fermentation liquid under moderate sulfate reduction.

In recent years, there has been a marked increase in the production of excess sludge. Chain-elongation (CE) fermentation presents a promising approach for carbon resource recovery from sludge, enabling the transformation of carbon into medium-chain fatty acids (MCFAs). However, the impact of sulfate, commonly presents in sludge, on the CE process remains largely unexplored. In this study, batch tests for CE process of sludge anaerobic fermentation liquid (SAFL) under different SCOD/SO42- ratios were performed. The moderate sulfate reduction under the optimum SCOD/SO42- of 20:1 enhanced the n-caproate production, giving the maximum n-caproate concentration, selectivity and production rate of 5.49 g COD/L, 21.4% and 4.87 g COD/L/d, respectively. The excessive sulfate reduction under SCOD/SO42- ≤ 5 completely inhibited the CE process, resulting in almost no n-caproate generation. The variations in n-caproate production under different conditions of SCOD/SO42- were all well fitted with the modified Gompertz kinetic model. Alcaligenes and Ruminococcaceae_UCG-014 were the dominant genus-level biomarkers under moderate sulfate reduction (SCOD/SO42- = 20), which enhanced the n-caproate production by increasing the generation of acetyl-CoA and the hydrolysis of difficult biodegradable substances in SAFL. The findings presented in this work elucidate a strategy and provide a theoretical framework for the further enhancement of MCFAs production from excess sludge.

Analysis of povidone iodine, chlorhexidine acetate and polyhexamethylene biguanide as wound disinfectants: in vitro cytotoxicity and antibacterial activity.

Objectives: Even though disinfectants are commonly used in clinical practice and daily life, there are few studies on their antibacterial ability and cytotoxicity, which are closely related to the safety and effectiveness of their use. To provide a basis for the use of disinfectants, the cytotoxicity and antibacterial activity of three most commonly used disinfectants, povidone-iodine, chlorhexidine acetate and polyhexamethylene biguanide (PHMB), were investigated. Design: A CCK-8 assay was used to measure the activities of human fibroblasts (HF) and keratinocytes (HaCat), the two most important cells in wound healing, following their exposure to disinfectants. The effects of different times and concentrations were included. The antibacterial activity of disinfectants against Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae was reflected by their minimum inhibitory concentration and minimum bactericidal concentration. Results: All three disinfectants showed strong cytotoxicity in direct contact with HF and HaCat cells. Cytotoxicity increased with increasing exposure time and concentration. S. aureus, A. baumannii and K. pneumoniae comprised 70%, 55% and 85% of the strains sensitive to povidone iodine; 50%, 45% and 80% of the strains sensitive to chlorhexidine acetate; and 60%, 45% and 80% of the strains sensitive to PHMB, respectively. Conclusions: All three disinfectants were cytotoxic; therefore, it is necessary to pay attention to the use time and concentration in the clinical setting. All three disinfectants were cytotoxic, with povidone-iodine being the most cytotoxic even at low concentrations. PHMB had better antibacterial efficacy against S. aureus and is suitable for the treatment of shallow wounds primarily. All three tested bacteria were significantly more sensitive to PHMB than to the other disinfectants.

A hyperthermophilic anaerobic fermentation platform for highly efficient short chain fatty acids production from thermal hydrolyzed sludge.

In this study, a carboxylate platform of hyperthermophilic (70 â„ƒ) anaerobic fermentation (HAF) for short chain fatty acids (SCFAs) production from thermal hydrolyzed sludge (THS) was established. The long-term performance for SCFAs production and the microbial communities of this HAF under different SRTs were systematically investigated. Under the optimum SRT of 3 d, the HAF had the highest acetate production rate of 1.12 g COD/L/d which accounted for 60% in SCFAs. It also rendered a good performance in SCFAs production, with concentration, production rate and yield of 6.61 g COD/L, 1.86 g COD/L/d and 324 g COD/kg VSSin, respectively. Nearly no biogas produced from this system, which reduced the loss of carbon sources from the system. This was due to the inhibition of methanogenesis by the hyperthermophilic condition and the high content of total ammonia nitrogen (TAN) and free ammonia nitrogen (FAN). Tepidimicrobium, Bhargavaea and XBB1006 were the dominant genus-level biomarkers under the optimum SRT, which facilitated the decomposition of monosaccharides, amino acids, terpenoids and polyketides into SCFAs. This work provides an applicable anaerobic carboxylate platform for highly efficient SCFAs production from excess sludge.

An adaptive neurodynamic approach for solving nonsmooth N-cluster games.

In this paper, N-cluster games with coupling and private constraints are studied, where each player's cost function is nonsmooth and depends on the actions of all players. In order to seek the generalized Nash equilibrium (GNE) of the nonsmooth N-cluster games, a distributed seeking neurodynamic approach with two-time-scale structure is proposed. An adaptive leader-following consensus technique is adapted to dynamically adjust parameters according to the degree of consensus violation, so as to quickly obtain accurate estimation information of other players' actions which facilitates the evaluation of its own cost. Benefitting from the unique structure of the approach based on primal dual and adaptive penalty methods, the players' actions enter the constraints while completing the seeking for GNE. As a result, the neurodynamic approach is completely distributed, and prior estimation of penalty parameters is avoided. Finally, two engineering examples of power system game and company capacity allocation verify the effectiveness and feasibility of the neurodynamic approach.

Subvacuum environment-enhanced cell migration promotes wound healing without increasing hypertrophic scars caused by excessive cell proliferation.

Cell migration and proliferation are conducive to wound healing; however, regulating cell proliferation remains challenging, and excessive proliferation is an important cause of scar hyperplasia. Here, we aimed to explore how a subvacuum environment promotes wound epithelisation without affecting scar hyperplasia. Human immortalized keratinocyte cells and human skin fibroblasts were cultured under subvacuum conditions (1/10 atmospheric pressure), and changes in cell proliferation and migration, target protein content, calcium influx, and cytoskeleton and membrane fluidity were observed. Mechanical calcium (Ca2+ ) channel blockers were used to prevent Ca2+ influx for reverse validation. A rat wound model was used to elucidate the mechanism of the subvacuum dressing in promoting healing. The subvacuum environment was observed to promote cell migration without affecting cell proliferation; intracellular Ca2+ concentrations and PI3K, p-PI3K, AKT1, p-AKT 1 levels increased significantly. The cytoskeleton was depolymerized, pseudopodia were reduced or absent, and membrane fluidity increased. The use of Ca2+ channel blockers weakened or eliminated these changes. Animal experiments confirmed these phenomena and demonstrated that subvacuum dressings can effectively promote wound epithelisation. Our study demonstrates that the use of subvacuum dressings can enhance cell migration without affecting cell proliferation, promote wound healing, and decrease the probability of scar hyperplasia.

Trehalose promotes functional recovery of keratinocytes under oxidative stress and wound healing via ATG5/ATG7.

Wounds are in a stressed state, which precludes healing. Trehalose is a stress metabolite that protects cells under stress. Here, we explored whether trehalose reduces stress-induced wound tissue damage. A stress model was prepared by exposing human keratinocytes to hydrogen peroxide (H2O2), followed by trehalose treatment. Trehalose effects on expression of the autophagy-related proteins ATG5 and ATG7 and cell proliferation and migration were evaluated. For in vivo verification, a wound model was established in Sprague-Dawley rats, to measure the effects of trehalose wound-healing rate and reactive oxygen species (ROS) content. Histological changes during wound healing and trehalose's effects on ATG5 and ATG7 expression, necrosis, and apoptosis were examined·H2O2 stress increased ATG5 and ATG7 expression in vitro, but this was insufficient to prevent stress-induced damage. Trehalose further increased ATG5/ATG7 levels, which restored proliferation and increased migration by depolymerizing the cytoskeleton. However, trehalose did not exert these effects after ATG5 and ATG7 knockout. In vivo, the ROS content was higher in the wound tissue than in normal skin. Trehalose increased ATG5/ATG7 expression in wound tissue keratinocytes, reduced necrosis, depolymerized the cytoskeleton, and promoted cell migration, thereby promoting wound healing.

A novel recombinant human collagen hydrogel as minced split-thickness skin graft overlay to promote full-thickness skin defect reconstruction.

To overcome limited donor-site availability in patients with extensive burns, split-thickness skin grafts (STSGs) are sometimes minced into micrografts (MGs) to improve the expansion ratio of the grafts, but this may reduce wound healing. We aimed to produce a novel hydrogel as an overlay of minced STSGs to improve wound healing. The new hydrogel was produced using recombinant human collagen type III powder as a raw material. Morphological and physical characteristics (degradation and swelling rate), cytotoxicity, and cell viability of the hydrogel were evaluated in vitro. A full-thickness in vivo skin defect model was constructed with male Sprague-Dawley rats. The animals were randomly assigned to experimental and control groups in which the new hydrogel and Vaseline gauze, respectively, were overlaid on minced STSGs to repair and regenerate skin wound. The healing rates and recovery status were compared between the two groups. The hydrogels exhibited good water retention properties and a suitable degradation rate, which can promote the proliferation and migration of wound healing-related cells in vitro. Further, using the hydrogel as an overlay accelerated wound closure and angiogenesis, increased dermal tissue and basement membrane formation, enhanced collagen synthesis and wound healing-related growth factor expression, while reducing scar formation compared to the Vaseline gauze group. In conclusion, the novel, low-cost recombinant human collagen hydrogel can accelerate wound closure and improve wound healing when used as an overlay of minced STSGs. The new hydrogel could become a new treatment option for traumatic skin wounds caused by burns or injuries.

Facilitating the Carrier Transport Kinetics at the CsPbBr3/Carbon Interface through SbX3 (X = Cl, Br, I) Passivation.

The nonradiative carrier recombination at the perovskite/carrier selective layer (CSL) interface was accounted for the inferior power conversion efficiency (PCE) of perovskite solar cells (PSCs), especially rigid all-inorganic perovskite (CsPbI3 and CsPbBr3). In this study, targeting the poor interface, we introduce SbX3 (X = Cl, Br, I) surface passivation at the CsPbBr3/carbon interface. Smoothed compressive strain, reduced defect density, and enhanced energy-level alignment were achieved simultaneously, facilitating carrier extraction at the selective interface. With the simple aqueous solution-based two-step process, the PCE of our SbI3 passivated carbon-based CsPbBr3 PSCs has increased from 7.81% (without passivation) to 9.69%, a ∼25% enhancement. Specifically, Voc (1.657 V) of the SbI3-passivated cells was much higher than that of the control ones (1.488 V), confirming the ameliorated interface. Finally, our unencapsulated SbI3 passivated devices maintain 90% of their initial PCEs while left in the air for 30 days with a relative humidity of 60%. To conclude, we present an interfacial carrier extraction-enhanced strategy for preparing high-performance and stable CsPbBr3-based PSCs.

Advances in regenerative medicine applications of tetrahedral framework nucleic acid-based nanomaterials: an expert consensus recommendation.

With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising nanostructures are tetrahedral framework nucleic acids (tFNAs), first proposed by Turberfield with the use of a one-step annealing approach. Benefiting from their various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, and editable functionality, tFNAs have been widely applied in the biomedical field as three-dimensional DNA nanomaterials. Surprisingly, tFNAs exhibit positive effects on cellular biological behaviors and tissue regeneration, which may be used to treat inflammatory and degenerative diseases. According to their intended application and carrying capacity, tFNAs could carry functional nucleic acids or therapeutic molecules through extended sequences, sticky-end hybridization, intercalation, and encapsulation based on the Watson and Crick principle. Additionally, dynamic tFNAs also have potential applications in controlled and targeted therapies. This review summarized the latest progress in pure/modified/dynamic tFNAs and demonstrated their regenerative medicine applications. These applications include promoting the regeneration of the bone, cartilage, nerve, skin, vasculature, or muscle and treating diseases such as bone defects, neurological disorders, joint-related inflammatory diseases, periodontitis, and immune diseases.

Therapeutic Effect and Mechanism of Negative Pressure Wound Therapy with Huoxue Shengji Decoction Instillation for Chronic Skin Ulcers.

Background: Negative pressure wound therapy (NPWT) with instillation (NPWTi) is a new treatment for chronic skin ulcers (CSUs), but the choice of perfusate is still investigated. The clinical application of Huoxue Shengji (HXSJ) decoction has been proved to promote the formation of granulation. The formation of fresh granulation, angiogenesis, and proliferation of vascular endothelial cells are closely related. The purpose of this study was to observe the clinical efficacy of NWPT with HXSJ decoction instillation in the treatment of CSUs and to explore the potential mechanism by which HXSJ decoction promotes proliferation of vascular endothelial cells at the cellular level. Methods: In the clinical study, the random number table was used to divide the patients into three groups (patients were numbered by visit time and assigned a random number and grouped by the remainder after the random number was divided by 3, and when the number of patients in one group reached 20, the enrolment of this group is stopped), including NPWT combined with HXSJ decoction instillation (group A), NPWT combined with normal saline instillation (group B), and NPWT (group C). Related indexes were examined, including the wound cavity volume, bacterial culture, histopathology examination, time periods of debridement, repair methods, and the time of ulcer healing. In the basic research, the effect of HXSJ decoction on the proliferation of HUVECs was analysed by CCK-8 assay and RT-PCR and western blot were used to quantify the VEGF and VEGFR-2 expression in the relevant signalling pathway. Results: There was no significant difference in the improvement rate of invasive cavity volume (P > 0.05) between groups A and B, but a significant difference was observed between groups A and C (P < 0.05). There was no significant difference in microbial reduction among groups (all P > 0.05). Histopathological examination showed that the microvascular count in group A was significantly higher than that in groups B and C (both P < 0.01) and there was no statistical difference between groups B and C (P > 0.05). There were no significant differences in the number of invasive lesions and repair methods among the groups (all P > 0.05). The healing time of group A was significantly faster than those of groups B and C (compared to group B, P < 0.05; compared to group C, P < 0.01), and there was no statistical difference between groups B and C (P > 0.05). In the cellular experiments, concentration screening was performed and 125 µg/mL HXSJ decoction showed the most significant effect on the proliferation of HUVECs and also enhanced the expression of VEGF and VEGFR-2. Conclusion: HXSJ decoction can enhance the expression of VEGF and VEGFR-2 and promote the proliferation of HUVECs. Treatment with NWPT with HXSJ decoction instillation can further reduce the wound cavity volume; meanwhile, it can promote blood vessel formation in ulcer wounds, thus accelerating the healing of CSUs.

Tetrahedral framework nucleic acids promote diabetic wound healing via the Wnt signalling pathway.

OBJECTIVES: To determine the therapeutic effect of tetrahedral framework nucleic acids (tFNAs) on diabetic wound healing and the underlying mechanism. MATERIALS AND METHODS: The tFNAs were characterized by polyacrylamide gel electrophoresis (PAGE), atomic force microscopy (AFM), transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential assays. Cell Counting Kit-8 (CCK-8) and migration assays were performed to evaluate the effects of tFNAs on cellular proliferation and migration. Quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the effect of tFNAs on growth factors. The function and role of tFNAs in diabetic wound healing were investigated using diabetic wound models, histological analyses and western blotting. RESULTS: Cellular proliferation and migration were enhanced after treatment with tFNAs in a high-glucose environment. The expression of growth factors was also facilitated by tFNAs in vitro. During in vivo experiments, tFNAs accelerated the healing process in diabetic wounds and promoted the regeneration of the epidermis, capillaries and collagen. Moreover, tFNAs increased the secretion of growth factors and activated the Wnt pathway in diabetic wounds. CONCLUSIONS: This study indicates that tFNAs can accelerate diabetic wound healing and have potential for the treatment of diabetic wounds.

Bioprinted Gelatin-Recombinant Type III Collagen Hydrogel Promotes Wound Healing.

Artificial skins are biomaterials that can replace the lost skin or promote the regeneration of damaged skin. Skin regenerative biomaterials are highly applauded because they can exempt patients with severe burns from the painful procedure of autologous skin transplantation. Notwithstanding decades of research, biocompatible, degradable, and printable biomaterials that can effectively promote skin regeneration as a transplantation replacement in clinical use are still scarce. Here, we report one type of all-protein hydrogel material as the product of the enzymatic crosslinking reaction of gelatin and a recombinant type III collagen (rColIII) protein. Doping the rColIII protein in gelatin reduces the inflammatory response as an implant underneath the skin. The all-protein hydrogel can be bioprinted as scaffolds to support the growth and proliferation of 3T3 fibroblast cells. The hydrogel used as a wound dressing promotes wound healing in a rat model of skin damage, showing a faster and healthier recovery than the controls. The rColIII protein in the hydrogel has been shown to play a critical role in skin regeneration. Altogether, this work manifests the development of all-protein gelatin-rColIII hydrogel and demonstrates its use in wound healing. The gelatin-collagen hydrogel wound dressing thereby may become a promising treatment of severe wounds in the future.

Differential translation elongation directs protein synthesis in response to acute glucose deprivation in yeast.

Protein synthesis is energetically expensive and its rate is influenced by factors such as cell type and environment. Suppression of translation is a canonical response to stressful changes in the cellular environment. In particular, inhibition of the initiation step of translation has been highlighted as the key control step in stress-induced translational suppression as mechanisms that quickly suppress initiation are well-conserved. However, cells have evolved complex regulatory means to control translation apart from initiation. Here, we examine the role of the elongation step of translation in yeast subjected to acute glucose deprivation. The use of ribosome profiling and in vivo reporter assays demonstrated elongation rates slow progressively following glucose removal. We observed that ribosome distribution broadly shifts towards the downstream ends of transcripts after both acute and gradual glucose deprivation but not in response to other stressors. Additionally, on assessed mRNAs, a correlation existed between ribosome occupancy and protein production pre-stress but was lost after stress. These results indicate that stress-induced elongation regulation causes ribosomes to slow down and build up on a considerable proportion of the transcriptome in response to glucose withdrawal. Finally, we report ribosomes that built up along transcripts are competent to resume elongation and complete protein synthesis after readdition of glucose to starved cells. This suggests that yeast has evolved mechanisms to slow translation elongation in response to glucose starvation which do not preclude continuation of protein production from those ribosomes, thereby averting a need for new initiation events to take place to synthesize proteins.Abbreviations: AUG: start codon, bp: base pair(s), CDS: coding sequence, CHX: cycloheximide, eEF2: eukaryotic elongation factor 2, LTM: lactimidomycin, nt: nucleotide, PGK1: 3-phosphoglycerate kinase, ribosomal biogenesis: ribi, RO: ribosome occupancy, RPF: ribosome protected fragment, TE: translational efficiency.

A self-crosslinking, double-functional group modified bacterial cellulose gel used for antibacterial and healing of infected wound.

Cellulose/chitosan composite, as a mature commercial antibacterial dressing, is an important type of wound repair material. However, how to achieve the perfect compound of two components and improve antibacterial activity is a major, lingering issue. In this study, a bifunctional group modified bacterial cellulose (DCBC) was prepared by carboxymethylation and selective oxidation. Further, the chitosan (CS) was compounded in the network of DCBC by self-crosslinking to form dialdehyde carboxymethyl bacterial cellulose/chitosan composites (S-DCBC/CS). The aldehyde group can react with amino of CS by Schiff base reaction. The carboxyl group of DCBC and the amorphous distribution of CS molecular chains increase the antimicrobial properties of composites. The bacteriostatic rate of composites could be higher than 95%. Bacteria can be attracted onto the surface of composites, what we call it "directional adhesion antibacterial effects". In particular, a kind of large animal wound model, deep Ⅱ degree infected scald of Bama miniature pig, was used to research the antimicrobial and healing properties of materials. The S-DCBC/CS can effectively inhibit bacterial proliferation of wound and kill the bacteria. The wound healing rate of S-DCBC/CS was up to 80% after three weeks. The composites show better antibacterial and promoting concrescence effects than traditional chitosan dressings.

Synergistic Effects of Quercetin-Modified Silicone Gel Sheet in Scar Treatment.

Both silicone gel and quercetin are effective in scar treatment but have different action mechanisms. Quercetin is mainly applied in the gel form and can lead to poor adhesion of silicone gel sheet; therefore, they cannot be combined in clinical use. In this study, a silicone gel sheet that releases quercetin in a sustained manner for 48 hours was successfully developed. Four round scars (Ø: 1 cm) were made in the ears of New Zealand albino rabbits (n = 10). After scar healing, the rabbits were divided into four groups: blank control group with no treatment, silicone gel sheet group with dressing change every 2 days, quercetin group with dressing change three times daily, and combination treatment group with dressing change every 2 days. Scar assessment was performed 3 months later. Transepidermal water loss showed no difference between the combination treatment group and the silicone gel sheet group, but was lower than that in the quercetin group and the blank control group. Immunohistochemistry of CD 31 and proliferating cell nuclear antigen showed the following results: combination treatment group < silicone gel sheet group = quercetin group < blank control group. Polymerase chain reaction results showed that the expression of type-I and type-III collagen in the combination treatment group and the quercetin group was significantly lower than that in the other two groups. Thus, quercetin-modified silicone gel sheet combines the advantages of the two treatments and is more effective at inhibiting cell proliferation in scar tissue than either of the two treatments alone.

Ablative fractional CO2 laser surgery improving sleep quality, pain and pruritus in adult hypertrophic scar patients: a prospective cohort study.

BACKGROUND: Poor sleep quality is associated with a decrease in quality of life in patients with major burn scars, combined with pruritus and pain. Few interventions have been reported to improve the sleep quality of patients with scars. In the current prospective cohort study, we investigated the efficacy of CO2-ablative fractional laser (AFL) surgery vs conventional surgery in post-burn patients with hypertrophic scars with sleep quality as the primary study outcome. METHODS: In total 68 consecutive patients undergoing scar surgical treatment were recruited, including a CO2-AFL surgery cohort (n = 35) and a conventional surgery cohort (n = 33). A subgroup from the AFL cohort was selected. Sleep quality, pain and pruritus were evaluated. Multiple linear regression analyses were performed to reveal the effect of CO2-AFL surgery. RESULTS: The CO2-AFL surgery cohort had significantly lower Pittsburgh sleep quality index (PSQI) global scores than the conventional surgery cohort after the last surgical treatment. In the subgroup of patients receiving hardware sleep monitoring, CO2-AFL markedly increased deep sleep time, deep sleep efficiency and reduced initial sleep latency. Compared to the conventional surgery cohort, the CO2-AFL cohort presented significantly lower pain and pruritus scores. Correlation analysis showed pain and pruritus were significantly associated with PSQI scores, and there were also significant correlations between pain and pruritus scores. Multiple linear regression analysis showed that surgery method was negatively linearly correlated with visual analog scale (VAS) pain score, brief pain inventory (BPI) total, VAS pruritus score, 5-D itch scale total, four-item itch questionnaire (FIIQ) total and PSQI total. CONCLUSIONS: CO2-AFL surgery significantly improved sleep quality and reduced pain and pruritus of hypertrophic scar patients. The alleviation of sleep disorder was associated with improvement of deep sleep quality including deep sleep time and deep sleep deficiency. TRIAL REGISTRATION: The Chinese Clinical Trial Registry (ChiCTR200035268) approved retrospectively registration on 5 May 2020.