From zinc homeostasis to disease progression: Unveiling the neurodegenerative puzzle.

Zinc is a crucial trace element in the human body, playing a role in various physiological processes such as oxidative stress, neurotransmission, protein synthesis, and DNA repair. The zinc transporters (ZnTs) family members are responsible for exporting intracellular zinc, while Zrt- and Irt-like proteins (ZIPs) are involved in importing extracellular zinc. These processes are essential for maintaining cellular zinc homeostasis. Imbalances in zinc metabolism have been linked to the development of neurodegenerative diseases. Disruptions in zinc levels can impact the survival and activity of neurons, thereby contributing to the progression of neurodegenerative diseases through mechanisms like cell apoptosis regulation, protein phase separation, ferroptosis, oxidative stress, and neuroinflammation. Therefore, conducting a systematic review of the regulatory network of zinc and investigating the relationship between zinc dysmetabolism and neurodegenerative diseases can enhance our understanding of the pathogenesis of these diseases. Additionally, it may offer new insights and approaches for the treatment of neurodegenerative diseases.

Protamine 1 as a secreted colorectal cancer-specific antigen facilitating G1/S phase transition under nutrient stress conditions.

PURPOSE: Cancer testis antigens (CTAs) are optimal tumor diagnostic markers and involved in carcinogenesis. However, colorectal cancer (CRC) related CTAs are less reported with impressive diagnostic capability or relevance with tumor metabolism rewiring. Herein, we demonstrated CRC-related CTA, Protamine 1 (PRM1), as a promising diagnostic marker and involved in regulation of cellular growth under nutrient deficiency. METHODS: Transcriptomics of five paired CRC tissues was used to screen CRC-related CTAs. Capability of PRM1 to distinguish CRC was studied by detection of clinical samples through enzyme linked immunosorbent assay (ELISA). Cellular functions were investigated in CRC cell lines through in vivo and in vitro assays. RESULTS: By RNA-seq and detection in 824 clinical samples from two centers, PRM1 expression were upregulated in CRC tissues and patients` serum. Serum PRM1 showed impressive accuracy to diagnose CRC from healthy controls and benign gastrointestinal disease patients, particularly more sensitive for early-staged CRC. Furthermore, we reported that when cells were cultured in serum-reduced medium, PRM1 secretion was upregulated, and secreted PRM1 promoted CRC growth in culture and in mice. Additionally, G1/S phase transition of CRC cells was facilitated by PRM1 protein supplementation and overexpression via activation of PI3K/AKT/mTOR pathway in serum deficient medium. CONCLUSIONS: In general, our research presented PRM1 as a specific CRC antigen and illustrated the importance of PRM1 in CRC metabolism rewiring. The new vulnerability of CRC cells was also provided with the potential to be targeted in future. Diagnostic value and grow factor-like biofunction of PRM1 A represents the secretion process of PRM1 regulated by nutrient deficiency. B represents activation of PI3K/AKT/mTOR pathway of secreted PRM1.

Application of Fullerenes as Photosensitizers for Antimicrobial Photodynamic Inactivation: A Review.

Antimicrobial photodynamic inactivation (aPDI) is a newly emerged treatment approach that can effectively address the issue of multidrug resistance resulting from the overuse of antibiotics. Fullerenes can be used as promising photosensitizers (PSs) for aPDI due to the advantages of high triplet state yields, good photostability, wide antibacterial spectrum, and permissibility of versatile functionalization. This review introduces the photodynamic activities of fullerenes and the up-to-date understanding of the antibacterial mechanisms of fullerene-based aPDI. The most recent works on the functionalization of fullerenes and the application of fullerene derivatives as PSs for aPDI are also summarized. Finally, certain remaining challenges are emphasized to provide guidance on future research directions for achieving clinical application of fullerene-based aPDI.

A credit risk assessment model of borrowers in P2P lending based on BP neural network.

Peer-to-Peer (P2P) lending provides convenient and efficient financing channels for small and medium-sized enterprises and individuals, and therefore it has developed rapidly since entering the market. However, due to the imperfection of the credit system and the influence of cyberspace restrictions, P2P network lending faces frequent borrower credit risk crises during the transaction process, with a high proportion of borrowers default. This paper first analyzes the basic development of China's P2P online lending and the credit risks of borrowers in the industry. Then according to the characteristics of P2P network lending and previous studies, a credit risk assessment indicators system for borrowers in P2P lending is formulated with 29 indicators. Finally, on the basis of the credit risk assessment indicators system constructed in this paper, BP neural network is built based on the BP algorithm, which is trained by the LM algorithm (Levenberg-Marquardt), Scaled Conjugate Gradient, and Bayesian Regularization respectively, to complete the credit risk assessment model. By comparing the results of three mentioned training methodologies, the BP neural network trained by the LM algorithm is finally adopted to construct the credit risk assessment model of borrowers in P2P lending, in which the input layer node is 9, the hidden layer node is 11 and output layer node is 1. The model can provide practical guidance for China and other countries' P2P lending platforms, and therefore to establish and improve an accurate and effective borrower credit risk management system.

Development of Poloxamer Hydrogels Containing Antibacterial Guanidine-Based Polymers for Healing of Full-Thickness Skin Wound.

A series of hydrogels containing guanidine-based polymers using a poloxamer as the matrix were prepared to provide novel wound dressings with antibacterial and repairing-promotion properties for skin wounds. Herein, we developed a series of antibacterial hydrogels, the cationic guanidine-based polymer polyhexamethylene guanidine hydrochloride (PHMG) with poloxamer aqueous solution (12%, w/w) simplified as PHMGP, chitosan (CS)-cross-linked PHMG (referred to as PHMC) with poloxamer aqueous solution simplified as PHMCP, and hyaluronic acid (HA)-modified PHMG (referred to as PHMH) with poloxamer aqueous solution simplified as PHMHP, for enhancing full-thickness skin wound healing. The characterizations, antimicrobial activity, cytotoxicity, and in vivo full-thickness wound-healing capability of these hydrogels were analyzed and evaluated. The results show that though PHMGP possesses great bactericide properties, its cytotoxicity is too strong to support skin regeneration. However, after modified with CS or HA, PHMCP and PHMHP showed good biocompatibility and antimicrobial properties against Gram-positive and Gram-negative bacteria that are commonly present in injured skin. Both PHMCP and PHMHP hydrogels exhibited upgraded wound-healing efficiency in full-thickness skin defects, characterized by a shorter wound closure time, faster re-regeneration, and the earlier formation of skin appendages, compared with those of control or pure poloxamer treatments. Their biological mechanism was detected. Both PHMCP and PHMHP can regulate the related biofactors during the skin repair process such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), transforming growth factor beta-1(TGF-ß1), alpha-smooth muscle actin (α-SMA), and vascular endothelial growth factor, to promote wound healing with less serious scarring. In short, hydrogels with excellent capabilities to inhibit microorganism infection and promote wound healing were developed, which will shed light on designing and producing wound dressings with promising applications in future.

Risk Factors for Transfusion-Related Acute Lung Injury.

BACKGROUND: Until now, transfusion-related acute lung injury (TRALI) has been considered the leading cause of blood transfusion-related diseases and death. In addition, there is no clinically effective treatment plan for TRALI. The aim of this study was to systematically summarize the literature on risk factors for TRALI in critical patients. METHODS: Electronic searches (up to March 2020) were performed in the Cochrane Library, Web of Knowledge, Embase, and PubMed databases. We included studies reporting on the risk factors of TRALI for critical patients and extracted risk factors. A total of 13 studies met the inclusion criteria. RESULTS: We summarized and analyzed the potential risk factors of TRALI for critical patients in 13 existing studies. Host-related factors were age (odds ratio [OR] 1.16 [95% CI 1.08-1.24]), female sex (OR 1.26 [95% CI 1.16-1.38]), tobacco use status (OR 3.82 [95% CI 1.91-7.65]), chronic alcohol abuse (OR 3.82 [95% CI 2.97-26.83]), positive fluid balance (OR 1.24 [95% CI 1.08-1.42]), shock before transfusion (OR 4.41 [95% CI 2.38-8.20]), and American Society of Anesthesiologists (ASA) score of the recipients (OR 2.72 [95% CI 1.43-5.16]). The transfusion-related factors were the number of transfusions (OR 1.40 [95% CI 1.14-1.72]) and units of fresh frozen plasma (OR 1.21 [95% CI 1.01-1.46]). The device-related factor was mechanical ventilation (OR 4.13 [95% CI 2.20-7.76]). CONCLUSIONS: The risk factors that were positively correlated with TRALI in this study included number of transfusions and units of fresh frozen plasma. Age, female sex, tobacco use, chronic alcohol abuse, positive fluid balance, shock before transfusion, ASA score, and mechanical ventilation may be potential risk factors for TRALI. Our results suggest that host-related risk factors may play a more important role in the occurrence and development of TRALI than risk factors related to blood transfusions.

Bacillus subtilis extracellular polymeric substances conditioning layers inhibit Escherichia coli adhesion to silicon surfaces: A potential candidate for interfacial antifouling additives.

Biofouling on material surfaces is a ubiquitous problem in a variety of fields. In aqueous environments, the process of biofouling initiates with the formation of a layer of macromolecules called the conditioning layer on the solid-liquid interface, followed by the adhesion and colonization of planktonic bacteria and the subsequent biofilm development and maturation. In this study, the extracellular polymeric substances (EPS) secreted by Bacillus subtilis were collected and used to prepare conditioning layers on inert surfaces. The morphologies and antifouling performances of the EPS conditioning layers were investigated. It was found that the initial adhesion of Escherichia coli was inhibited on the surfaces precoated with EPS conditioning layers. To further explore the underlying antifouling mechanisms of the EPS conditioning layers, the respective roles of two constituents of B. subtilis EPS (γ-polyglutamic acid and surfactin) were investigated. This study has provided the possibility of developing a novel interfacial antifouling additive with the advantages of easy preparation, nontoxicity, and environmental friendliness.

Non-muscle myosin II knockdown improves survival and therapeutic effects of implanted bone marrow-derived mesenchymal stem cells in lipopolysaccharide-induced acute lung injury.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to have some beneficial effects in acute lung injury (ALI), but the therapeutic effects are limited due to apoptosis or necrosis after transplantation into injured lungs. Here, we aim to explore whether Non-muscle myosin II (NM-II) knockdown could enhance BMSCs survival and improve therapeutic effects in ALI. METHODS: MSCs, isolated from rat bone marrow, were transfected with the small interfering RNA (siRNA) targeted to NM-II mRNA by a lentivirus vector. Rats were equally randomized to four groups: the control group was given normal saline via tail vein; the other three groups underwent intratracheal lipopolysaccharide (LPS) instillation followed by administration with either normal saline, BMSCs transduced with lentivirus-enhanced green fluorescent protein (eGFP) empty vector, or BMSCs transduced with lentivirus-eGFP NM-II siRNA. Hematoxylin and eosin staining was used to evaluate lung histopathologic changes and Masson trichrome staining was used to assess lung fibrosis. The myeloperoxidase activity was also tested in lung tissues. The mRNA expression of inflammatory cytokines in lung tissues was determined via quantitative reverse transcription PCR. Sex-determining region of the Y chromosome gene expression was measured by fluorescence in situ hybridization (FISH) assay. The expression of self-renewal activity and apoptosis-associated proteins were measured by Western blot. RESULTS: Transplantation of NM-II siRNA-modified BMSCs could improve histopathological morphology, decrease inflammatory infiltrates, down-regulate the expression levels of inflammatory cytokines, and reduce pulmonary interstitial edema. NM-II siRNA-modified BMSCs showed antifibrotic properties and alleviated the degrees of pulmonary fibrosis induced by endotoxin. In addition, NM-II knockdown BMSCs showed slightly better therapeutic effect on lung inflammation when compared with control BMSCs. The beneficial effects of NM-II siRNA-modified BMSCs may be attributed to enhanced self-renewal activity and decreased apoptosis. CONCLUSIONS: NM-II knockdown could inhibit the apoptosis of implanted BMSCs in lung tissues and improve its self-renewal activity. NM-II siRNA-modified BMSCs have a slightly enhanced ability to attenuate lung injury after LPS challenge.

A recombinant human collagen hydrogel for the treatment of partial-thickness burns: A prospective, self-controlled clinical study.

INTRODUCTION: Allogeneic and xenogeneic skin are recognized as the best coverings for skin burn wounds, but currently face a supply shortage. To solve this problem, our research group developed a standardized manufactured hydrogel dressing based on a new type of highly bioactive recombinant human collagen. STUDY DESIGN: Prospective self-controlled trial. OBJECTIVE: To evaluate the efficacy and safety of recombinant human collagen hydrogel in the treatment of partial burn wounds to the skin compared to those of xenogeneic skin. METHODS: This study included twenty-one patients admitted to Shanghai Changhai Hospital within 48 h after receiving partial-thickness skin burns. The wounds were symmetrically separated along the axis and treated with recombinant human collagen hydrogel (RHCH) or a human-CTLA4-Ig gene-transferred pig skin xenotransplant. The condition of the wound surfaces was recorded on days 0 (of enrollment), 5, 10, 15, and 20, and bacterial drug sensitivity testing, hematuria examination, and electrocardiographic tests were conducted on days 0, 10, 20, or on the day of wound healing. RESULTS: There were no statistically significant differences in wound healing time between the two groups. The median number of days to healing was 11.00 ± 0.56 for xenogeneic skin vs. 11.00 ± 1.72 for RHCH. CONCLUSION: During the observation period, the therapeutic effect of the RHCH developed by our group on partial-thickness burn wounds was not significantly different from that of gene-transferred xenogeneic skin. Thus, our designed RHCH shows potential for clinical use to treat burn wounds on the skin.

Admission Neutrophil-Lymphocyte Ratio (NLR) Predicts Survival in Patients with Extensive Burns.

BACKGROUND: Extensive burns is one of the most common severe injuries, with a high annual death rate. Previous studies showed that the neutrophil to lymphocyte ratio (NLR) is a prognostic factor for some inflammatory diseases. However, until now, no study has evaluated the clinical prognostic value of NLR in extensively burned patients. The aim of this study was to investigate the prognostic value of NLR in this medical condition to provide clinical guidance. METHODS: 271 patients diagnosed with extensive burns were analysed retrospectively between 2005 and 2018 in the Department of Burn Surgery of Changhai Hospital. NLR cut-off values at the first 3 days of hospitalization were calculated by the ROC analysis. RESULTS: Of the 271 patients in this study, the majority (82.3%) were injured by flame. The median total body surface area (TBSA) was 55% (IQR, 40% to 85%) and the median full thickness burn (FTB) was 20% (IQR, 3%-44%). The patients' NLR declined within the first 3 days after admission, and we found that NLR was negatively correlated with the ventilator-free days at day 28 (r = -0.127, P = 0.048). In a multivariate logistic regression analysis, higher admission NLR was independently predictive of higher mortality. According to the ROC curve, the best cut-off values for day 1 (or admission day), day 2 and day 3 NLR were 14, 13 and 7.5, respectively. We then performed a survival analysis, finding that those NLR above the cut-off point had decreased overall survival compared to those with NLR below the cut-off point (p = 0.023, 0.045 and 0.019 for day 1, 2, and 3, respectively). CONCLUSIONS: NLR continuously decreased in the first 3 days of hospitalization. Admission NLR above 14 is associated with a decreased survival in patients with extensive burns. These findings demonstrate that NLR has prognostic value in these patients.

The Mechanisms and the Applications of Antibacterial Polymers in Surface Modification on Medical Devices.

Medical device contamination caused by microbial pathogens such as bacteria and fungi has posed a severe threat to the patients' health in hospitals. Due to the increasing resistance of pathogens to antibiotics, the efficacy of traditional antibiotics treatment is gradually decreasing for the infection treatment. Therefore, it is urgent to develop new antibacterial drugs to meet clinical or civilian needs. Antibacterial polymers have attracted the interests of researchers due to their unique bactericidal mechanism and excellent antibacterial effect. This article reviews the mechanism and advantages of antimicrobial polymers and the consideration for their translation. Their applications and advances in medical device surface coating were also reviewed. The information will provide a valuable reference to design and develop antibacterial devices that are resistant to pathogenic infections.

The Impact of Blood Type O on Major Outcomes in Patients With Severe Burns.

ABO blood type has been reported to be a predictor of poor prognosis in critically ill patients. Here, we aim to correlate different blood types with clinical outcomes in patients with severe burns. We conducted a single-center retrospective cohort study by enrolling patients with severe burn injuries (≥40% TBSA) between January 2012 and December 2017. Baseline characteristics and clinical outcomes were compared between disparate ABO blood types (type O vs non-O type). Multivariate logistic and linear regression analyses were performed to identify an association between ABO blood type and clinical outcomes, including in-hospital mortality, the development of acute kidney injury (AKI), and hospital or ICU length of stay. A total of 141 patients were finally enrolled in the current study. Mortality was significantly higher in patients with type O blood compared with those of other blood types. The development of AKI was significantly higher in patients with blood type O vs non-O blood type (P = .001). Multivariate analysis demonstrated that blood type O was independently associated with in-hospital mortality and AKI occurrence after adjusting for other potential confounders. Our findings indicated the blood type O was an independent risk factor of both increased mortality and the development of AKI postburn. More prudent and specific treatments are required in treating these patients to avoid poor prognosis.

Preadsorption of Serum Proteins Regulates Bacterial Infections and Subsequent Macrophage Phagocytosis on Biomaterial Surfaces.

Bacterial infection has been one of the main obstacles for extensive biomedical applications of biomaterial films. Understanding the interactions among macromolecules, cells, and bacteria in the microenvironment located on the film surface at the molecular level is essential for developing antibacterial films. Here we report the distinct influence of several key serum proteins adsorbed on diamond-like carbon (DLC) and traditional Ti films on initial bacterial adhesion, biofilm formation, and corresponding immune responses. Type I collagen, Fn, and IgG were selected as the typical serum proteins. Gram-positive bacterium Staphylococcus epidermidis and Gram-negative bacterium Escherichia coli were used as the model bacteria. Macrophage phagocytosis tests were carried out to examine the impact of adsorbed proteins on the ability of macrophages to clear the adhered pathogens. Results show that it was the specific molecular recognition between adsorbed proteins and bacteria, not the surface physiochemical properties such as surface wettability, surface roughness, and surfaces charge, that decisively affected bacterial adhesion and following biofilm formation. Collagen resisted bacterial adhesion on both DLC and Ti films, even though the molecules exhibited distinct conformations on the two surfaces, whereas for Fn and IgG, the specific molecular recognition was closely related to protein conformations. Fn molecules formed globular aggregates on Ti surfaces that greatly enhanced bacterial adhesion but exhibited a fibril conformation on DLC surfaces that inhibited bacterial adhesion. IgG showed an end-on orientation with free F(ab)2 domains on Ti surfaces, facilitating bacterial adhesion and biofilm formation, while the flattened orientation on DLC films showed little effect on bacterial behaviors. Furthermore, preadsorption of Fn and IgG significantly promoted the phagocytosis ability of macrophages against S. epidermidis and affected the corresponding secretion of inflammatory cytokine. These results would give insights into understanding protein-surface interactions for developing appropriate surface modification techniques for biomaterials with desired anti-inflammatory functions.

Adsorption-associated orientational changes of immunoglobulin G and regulated phagocytosis of Staphylococcus epidermidis.

Understanding the adsorption of immunoglobulin G (IgG) on biomaterials surfaces is crucial for design and modification of the surfaces to alleviate inflammatory responses after implantation. Here, we report direct visualization and two-dimensional (2D) image interpretation of the IgG molecule adsorbed on simplified surfaces by single particle electron microscopy and atomic force microscopy. Influence of the orientational changes in adsorbed IgG on phagocytosis of macrophages against Staphylococcus epidermidis is further examined. Untreated amorphous carbon film and -COOH and -NH2 grafted carbon films are employed as the model surfaces for the adsorption testing. Results show that IgG displays flat orientation lying on the untreated surface, while forms vertical orientations standing on the functionalized surfaces. These specific spatial alignments are associated with altered unfolding extent and structure rearrangement of IgG domains, which are influenced synergistically by surface charge and wettability of the substrata. The changes in interdomain distance of IgG molecules subsequently regulate immune behaviors of macrophages and phagocytosis of S. epidermidis. The results would give insight into appropriate design of biomaterial surfaces in nanoscales for desired inflammatory responses. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2838-2849, 2018.

[Impacts of climate warming on growth period and yield of rice in Northeast China during recent two decades].

By using rice growth period, yield and climate observation data during the recent two decades, the impact of climate warming on rice in Northeast China was investigated by mathematical statistics methods. The results indicated that in the three provinces of Northeast China, the average, maximum and minimum temperatures in rice growing season were on the. rise, and the rainfall presented a downward trend during 1989-2009. Compared to 1990s, the rice whole growth periods of Heilongjiang, Jilin and Liaoning provinces in 2000s were prolonged 14 d, 4.5 d and 5.1 d, respectively. The increase of temperature in May, June and September could extend the rice growth period, while that in July would shorten the growth duration. The rice growth duration of registered varieties and experiment sites had a similar increasing trend in Northeast China except for the Heilongjiang Province, and the extension of registered varieties growth period was the main factor causing the prolonged growth period of rice at experiment sites. The change in daily average, minimum and maximum temperatures all could affect the rice yield in Northeast China. The increasing temperature significantly increased the rice yield in Heilongjiang Province, especially in the west region of Sanjiang Plain. Except for the south of Liaoning Province, rice yields in other regions of Northeast China were promoted by increasing temperature. Proper measures for breeding, cultivation and farming, could be adopted to fully improve the adaptation of rice to climate warming in Northeast China.

Highly efficient and recyclable carbon soot sponge for oil cleanup.

Carbon soot (CS) has the advantages of cost-effectiveness and production scalability over other carbons (i.e., graphene, CNTs) in their synthesis. However, little research has been conducted to explore the potential applications of CS. In this study, we demonstrated that a common daily waste-CS-can be used for developing a cost-effective absorbent (CS-sponge) to remove oil contaminants from water. The CS was synthesized by an ethylene-oxygen combustion flame. The CS-sponge was prepared via a dip-coating method. Without further surface modification and pretreatments, the CS-sponge demonstrates high absorption capacities (up to 80 times its own weight) for a broad spectrum of oils and organic solvents with a recyclability of more than 10 times. These research results show evidence that the CS-sponge is promising in environmental remediation for large-scale, low-cost removal of oils from water.