Ameliorative Effect of Natural Sesquiterpene Alcohol Cedrol Against Cerebral Ischemia Infarction-In Vitro and In Vivo Studies.

Cedrol is a major bioactive compound present in the Cedrus atlantica with numerous biological properties. In this study, we elucidated the neuroprotective properties of cedrol against ischemic infarction in animal and in vitro studies. A cerebral ischemic/reperfusion model was induced in adult Wistar rats, and oxygen-glucose deprivation/reperfusion was induced in SH-SY5Y neuronal cells and treated with different concentrations of cedrol. The percentage of water content, cerebral  infarct, and neurological deficit score was assessed in experimental rats. The acetylcholinesterase activity and inflammatory cytokines were quantified to analyze the anti-inflammatory potency of cedrol. Oxidative stress marker malondialdehyde and antioxidants were quantified to evaluate the antioxidant potency of cedrol in an ischemic condition. The neuroprotective potency of cedrol was confirmed by histopathological analysis of the brain tissue of cedrol-treated I/R-induced rats. In in vitro studies, the MTT and LDH assays were performed in cedrol-treated OGD/R SH-SY5Y cells to analyze the cytoprotective effect of cedrol. The anti-inflammatory property of cedrol was confirmed by quantifying the pro-inflammatory cytokine levels in OGD/R-induced cedrol-treated SH-SY5Y cells. The results obtained prove that cedrol significantly prevents brain edema, neurological deficits, acetylcholinesterase activity, and oxidative damage in ischemic-induced rats. It inhibited neuroinflammation in ischemic-induced rats and also in in vitro models. The neuroprotective effect of cedrol during an ischemic condition was authentically established with histological analysis in an animal model and cell survival assays in an in vitro model. Overall, our results confirm that cedrol is a potent alternative drug to treat cerebral ischemia in the future.

Spatiotemporal orchestration of macrophage activation trajectories by Vγ4 T cells during skin wound healing.

Dysregulated macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotypes underlies impaired cutaneous wound healing. This study reveals Vγ4+ γδ T cells spatiotemporally calibrate macrophage trajectories during skin repair via sophisticated interferon-γ (IFN-γ) conditioning across multiple interconnected tissues. Locally within wound beds, infiltrating Vγ4+ γδ T cells directly potentiate M1 activation and suppress M2 polarization thereby prolonging local inflammation. In draining lymph nodes, infiltrated Vγ4+ γδ T cells expand populations of IFN-γ-competent lymphocytes which disseminate systemically and infiltrate into wound tissues, further enforcing M1 macrophages programming. Moreover, Vγ4+γδ T cells flushed into bone marrow stimulate increased IFN-γ production, which elevates the output of pro-inflammatory Ly6C+monocytes. Mobilization of these monocytes continually replenishes the M1 macrophage pool in wounds, preventing phenotypic conversion to M2 activation. Thus, multi-axis coordination of macrophage activation trajectories by trafficking Vγ4+ γδ T cells provides a sophisticated immunological mechanism regulating inflammation timing and resolution during skin repair.

[Analysis of a case of Kabuki syndrome due to a novel variant of KMT2D gene].

OBJECTIVE: To report on a case of Kabuki syndrome (KS) due to a novel variant of KMT2D gene. METHODS: A child diagnosed with KS at the Fujian Children's Hospital on July 25, 2022 was selected as the study subject. Whole exome sequencing was carried out for the child and her parents. Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 4-month-old female, had presented with distinctive facial features, growth retardation, cardiac malformations, horseshoe kidney, hypothyroidism, and recurrent aspiration pneumonia. Whole exome sequencing revealed that she has harbored a heterozygous c.6285dup (p.Lys2096Ter) variant of the KMT2D gene. Sanger sequencing confirmed that neither of her parents had carried the same variant. The variant was previously unreported and may result in a truncated protein and loss of an enzymatic activity region. The corresponding site of the variant is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The c.6285dup variant of the KMT2D gene probably underlay the KS in this child.

Predicting COVID-19 Re-Positive Cases in Malnourished Older Adults: A Clinical Model Development and Validation.

Purpose: Building and validating a clinical prediction model for novel coronavirus (COVID-19) re-positive cases in malnourished older adults. Patients and Methods: Malnourished older adults from January to May 2023 were retrospectively collected from the Department of Geriatrics of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. They were divided into a "non-re-positive" group and a "re-positive" group based on the number of COVID-19 infections, and into a training set and a validation set at a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify predictive factors for COVID-19 re-positivity in malnourished older adults, and a nomogram was constructed. Independent influencing factors were screened by multivariate logistic regression. The model's goodness-of-fit, discrimination, calibration, and clinical impact were assessed by Hosmer-Lemeshow test, area under the curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CIC), respectively. Results: We included 347 cases, 243 in the training set, and 104 in the validation set. We screened 10 variables as factors influencing the outcome. By multivariate logistic regression analysis, preliminary identified protective factors, risk factors, and independent influencing factors that affect the re-positive outcome. We constructed a clinical prediction model for COVID-19 re-positivity in malnourished older adults. The Hosmer-Lemeshow test yielded χ2 =5.916, P =0.657; the AUC was 0.881; when the threshold probability was >8%, using this model to predict whether malnourished older adults were re-positive for COVID-19 was more beneficial than implementing intervention programs for all patients; when the threshold was >80%, the positive estimated value was closer to the actual number of cases. Conclusion: This model can help identify the risk of COVID-19 re-positivity in malnourished older adults early, facilitate early clinical decision-making and intervention, and have important implications for improving patient outcomes. We also expect more large-scale, multicenter studies to further validate, refine, and update this model.

Rice false smut virulence protein subverts host chitin perception and signaling at lemma and palea for floral infection.

The flower-infecting fungus Ustilaginoidea virens causes rice false smut, which is a severe emerging disease threatening rice (Oryza sativa) production worldwide. False smut not only reduces yield, but more importantly produces toxins on grains, posing a great threat to food safety. U. virens invades spikelets via the gap between the two bracts (lemma and palea) enclosing the floret and specifically infects the stamen and pistil. Molecular mechanisms for the U. virens-rice interaction are largely unknown. Here, we demonstrate that rice flowers predominantly employ chitin-triggered immunity against U. virens in the lemma and palea, rather than in the stamen and pistil. We identify a crucial U. virens virulence factor, named UvGH18.1, which carries glycoside hydrolase activity. Mechanistically, UvGH18.1 functions by binding to and hydrolyzing immune elicitor chitin and interacting with the chitin receptor CHITIN ELICITOR BINDING PROTEIN (OsCEBiP) and co-receptor CHITIN ELICITOR RECEPTOR KINASE1 (OsCERK1) to impair their chitin-induced dimerization, suppressing host immunity exerted at the lemma and palea for gaining access to the stamen and pistil. Conversely, pretreatment on spikelets with chitin induces a defense response in the lemma and palea, promoting resistance against U. virens. Collectively, our data uncover a mechanism for a U. virens virulence factor and the critical location of the host-pathogen interaction in flowers and provide a potential strategy to control rice false smut disease.

Platelet Vesicles Synergetic with Biosynthetic Cellulose Aerogels for Ultra-Fast Hemostasis and Wound Healing.

Achieving hemostasis in penetrating and irregular wounds is challenging because the hemostasis factor cannot arrive at the bleeding site, and substantial bleeding will wash away the blood clot. Since the inherently gradual nature of blood clot formation takes time, a physical barrier is needed before blood clot formation. Herein, an ultra-light and shape memory hemostatic aerogel consisting of oxidized bacterial cellulose (OBC) and platelet extracellular vesicles (pVEs) is reported. The OBC-pVEs aerogel provides a physical barrier for the bleeding site by self-expansion, absorbing the liquid from blood to concentrate platelets and clotting factors and accelerating the clot formation by activating platelets and transforming fibrinogen into fibrin. In the rat liver and tail injury models, the blood loss decreases by 73% and 59%, and the bleeding times are reduced by 55% and 62%, respectively. OBC-pVEs aerogel has also been shown to accelerate wound healing. In conclusion, this work introduces an effective tool for treating deep, non-compressible, and irregular wounds and offers valuable strategies for trauma bleeding and wound treatment.

A Census Tract-Level Examination of Diagnosed HIV Infection and Social Vulnerability Themes Among Black/African American, Hispanic/Latino, and White Adults, 2019-USA.

BACKGROUND: Assessing HIV diagnosis and the social vulnerability index (SVI) by themes (socioeconomic status, household composition and disability, minority status and English proficiency, and housing type and transportation) might help to identify specific social factors contributing to disparities across census tracts with high rates of diagnosed HIV infection in the USA. METHODS: We examined HIV rate ratios in 2019 using data from CDC's National HIV Surveillance System (NHSS) for Black/African American, Hispanic/Latino, and White persons aged ≥ 18 years. NHSS data were linked to CDC/ATSDR SVI data to compare census tracts with the lowest SVI (Q1) and highest SVI (Q4) scores. Rates and rate ratios were calculated for 4 SVI themes by sex assigned at birth for age group, transmission category, and region of residence. RESULTS: In the socioeconomic theme analysis, we observed wide within-group disparity among White females with diagnosed HIV infection. In the household composition and disability theme, we observed high HIV diagnosis rates among Hispanic/Latino and White males who lived in the least socially vulnerable census tracts. In the minority status and English proficiency theme, we observed a high percentage of Hispanic/Latino adults with diagnosed HIV infection in the most socially vulnerable census tracts. In the housing type and transportation theme, we observed a high percentage of HIV diagnoses attributed to injection drug use in the most socially vulnerable census tracts. CONCLUSION: The development and prioritization of interventions that address specific social factors contributing to disparities in HIV across census tracts with high diagnosis rates are critical to reducing new HIV infections in the USA.

Physiological and transcriptomic response reveals new insight into manganese tolerance of Celosia argentea Linn.

Celosia argentea is a manganese (Mn) hyperaccumulator with high ornamental value and strong stress resistance. It is important to understand the molecular mechanism of tolerance to heavy metals of hyperaccumulators to improve the efficiency of phytoremediation. In this study, the effects of different Mn concentrations (0, 0.8, 3, and 10 mM) on physiological characteristics and molecular changes were determined. Low concentrations of Mn increased the growth of C. argentea, while high concentrations of Mn suppressed its growth, A concentration up to 3 mM did not affect the growth of C. argentea, and the highest transfer factor (TF) was 6.16. Oxidative damage of different Mn level treatments in C. argentea was verified through relative water content, electrolyte leakage, MDA content, H2O2 content and superoxide contents. With an increase in Mn concentration, the contents of chlorophyll a, chlorophyll b, and carotenoids decreased. Our results indicated that low-concentration manganese treatment can reduce the reactive oxygen burst and MDA, soluble sugar and proline, making C. argentea have strong abiotic stress tolerance. The molecular mechanism of C. argentea after 10 mM Mn treatment was analysed through transcriptome analysis, and differentially expressed genes (DEGs) in these pathways were further verified by qRTPCR. Plantpathogen interactions, plant hormone signal transduction, the MAPK signalling pathway and the phenylpropanoid biosynthesis pathway were important in the response to Mn stress, and the heavy metal-associated isoprenylated plant protein, metal transporter Nramp, and zinc transporter play key roles in the strong ability of C. argentea to tolerate heavy metals. These results suggest that C. argentea exhibits strong manganese tolerance and provide new insight into the molecular mechanisms of plant responses to heavy metal stress.

Particle-Scale Understanding of Arsenic Interactions with Sulfidized Nanoscale Zerovalent Iron and Their Impacts on Dehalogenation Reactivity.

Co-occurrence of organic contaminants and arsenic oxoanions occurs often at polluted groundwater sites, but the effect of arsenite on the reactivity of sulfidized nanoscale zerovalent iron (SNZVI) used to remediate groundwater has not been evaluated. Here, we study the interaction of arsenite [As(III)] with SNZVI at the individual-particle scale to better understand the impacts on the SNZVI properties and reactivity. Surface and intraparticle accumulation of As was observed on hydrophilic FeS-Fe0 and hydrophobic FeS2-Fe0 particles, respectively. X-ray absorption spectroscopy indicated the presence of realgar-like As-S and elemental As0 species at low and high As/Fe concentration ratios, respectively. Single-particle inductively coupled plasma time-of-flight mass spectrometry analysis identified As-containing particles both with and without Fe. The probability of finding As-containing particles without Fe increased with the S-induced hydrophobicity of SNZVI. The interactions of SNZVI materials with coexisting arsenite inhibited their reactivity with water (∼5.8-230.7-fold), trichloroethylene (∼3.6-67.5-fold), and florfenicol (∼1.1-5.9-fold). However, the overall selectivity toward trichloroethylene and florfenicol relative to water was improved (up to 9.0-fold) because the surface-associated As increased the SNZVI hydrophobicity. These results indicate that reactions of SNZVI with arsenite can remove As from groundwater and improve the properties of SNZVI for dehalogenation selectivity.

Tunable Sulfated Alginate-based Hydrogel Platform with enhanced anti-inflammatory and antioxidant capacity for promoting burn wound repair.

Amidst progressive advancements in tissue engineering, there has been a significant enhancement in the efficacy of anti-inflammatory hydrogel dressings, addressing a myriad of clinical challenges on wound healing. A frequent complication during the initial stages of deep second-degree burn wound healing is the onset of an inflammatory storm, typically occurring without effective intervention. This event disrupts normal biological healing sequences, leading to undesirable regression. In response, we have customized a tunable, multidimensional anti-inflammatory hydrogel platform based on sulfated alginates (Algs), loaded with Prussian blue (PB) nanozymes. This platform competently eliminates surplus reactive oxygen species (ROS) present in the wound bed. Algs, functioning as a mimic of sulfated glycosaminoglycans (including heparin, heparan sulfate, and chondroitin sulfate) in the extracellular matrices (ECM), demonstrate a high affinity towards inflammatory chemokines such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1). This affinity effectively impedes the infiltration of inflammatory cells into the wound. Concurrently, Algs markedly modulate the macrophage phenotype transition from M1 to M2. Ultimately, our potent anti-inflammatory hydrogels, which strategically target inflammatory chemokines, M1 macrophages, and ROS, successfully attenuate dysregulated hyperinflammation in wound sites. Precise immunomodulation administered to deep second-degree burn wounds in mice has demonstrated promotion of neovascular maturation, granulation tissue formation, collagen deposition, and wound closure. Our biomimetic hydrogels, therefore, represent a significant expansion in the repertoire of anti-inflammatory strategies available for clinical practice.

Association of serum levels of vascular endothelial growth factor and placental growth factor in early threatened abortion and premature delivery: A case­control study.

Vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) serve key roles in the regulation of vascular development, revascularization and vasopermeability in the endometrium, decidua and trophoblasts. Furthermore, both VEGF and PlGF are modulators of embryonic vascular development. Thus, the present study aimed to investigate the serum levels of VEGF and PlGF in female patients with early threatened abortion (TA) who experienced preterm delivery. The present case-control study included 130 pregnant patients with or without TA that were admitted to The Maternal and Childcare Hospital of Nantong University from January 2019 to January 2022. Patients were divided into two groups: i) Group A, which included 55 patients diagnosed with TA with slight vaginal bleeding and closed cervical internal os within the first 6-12 weeks of pregnancy; and ii) group B, which included 75 patients with healthy asymptomatic pregnancy. Blood samples were obtained from all patients and VEGF and PlGF levels were examined prior to treatment, and the chi-squared, Student's t-test and two-way ANOVA followed by Bonferroni's post hoc analysis were used to analyze statistical differences between the two patient groups. Results of the present study demonstrated that patients with TA had significantly lower levels of VEGF and PlGF, compared with the controls. In patients with or without TA, the levels of serum PlGF in the preterm delivery group were significantly decreased compared with patients that did not experience preterm delivery. However, there was no significant difference in the levels of VEGF between patients with or without preterm delivery. In addition, lower levels of PlGF, compared with those in patients without TA, may be associated with an increased risk of preterm delivery in patients without early TA.

Tailoring Fe0 Nanoparticles via Lattice Engineering for Environmental Remediation.

Lattice engineering of nanomaterials holds promise in simultaneously regulating their geometric and electronic effects to promote their performance. However, local microenvironment engineering of Fe0 nanoparticles (nFe0) for efficient and selective environmental remediation is still in its infancy and lacks deep understanding. Here, we present the design principles and characterization techniques of lattice-doped nFe0 from the point of view of microenvironment chemistry at both atomic and elemental levels, revealing their crystalline structure, electronic effects, and physicochemical properties. We summarize the current knowledge about the impacts of doping nonmetal p-block elements, transition-metal d-block elements, and hybrid elements into nFe0 crystals on their local coordination environment, which largely determines their structure-property-activity relationships. The materials' reactivity-selectivity trade-off can be altered via facile and feasible approaches, e.g., controlling doping elements' amounts, types, and speciation. We also discuss the remaining challenges and future outlooks of using lattice-doped nFe0 materials in real applications. This perspective provides an intuitive interpretation for the rational design of lattice-doped nFe0, which is conducive to real practice for efficient and selective environmental remediation.

Effects of edaravone dexborneol on neurological function and serum inflammatory factor levels in patients with acute anterior circulation large vessel occlusion stroke.

The goal of this study is to evaluate and analyze the effects of edaravone (EDV) dexborneol on neurological function and serum inflammatory factor levels among patients with acute anterior circulation big artery blockage stroke. A total of 142 patients with acute anterior circulation large vessel occlusion (LVO) were randomly allocated to the study group (69 patients) or the control group (73 patients). In the study group, patients were treated with 37.5 mg EDV dexborneol twice a day for 10-14 days, based on the control group. The primary efficacy outcome was the National Institutes of Health Stroke Scale score change from baseline to 90 days and the proportion of modified Rankin Scale (mRS)score ≤1 at 90 days after randomization. The secondary outcome included the decrease in inflammatory factors at 14 days. The primary safety outcome was the incidence of hemorrhagic transformation assessed according to Heidelberg bleeding classification within 7 days. A higher percentage of patients with HIHSS score ≤5 at 90 days in the EDV dexcamphorol group was observed than in the control group (75.36% vs 64.38%; P = 0.015). A higher percentage of patients with mRS score ≤1 at 90 days in the EDV dexcamphorol group was observed than in the control group (63.77% vs 50.68%; P = 0.012). After treatment, the levels of IL-6 and hs-CRP were significantly lower following treatment and compared to the control group (P < 0.05). In patients receiving the EDV dexborneol group, a significantly decreased risk of radiographic intracranial hemorrhage was found compared with the control group (20.29% vs 39.73%; P = 0.0006). In conclusion, EDV dexborneol can improve the clinical outcomes of patients with acute anterior circulation LVO stroke, which can be used as an effective supplement to thrombectomy therapy.

Diurnal Characteristics of the Orexin System Genes and Its Effects on Pathology at Early Stage in 3xTg-AD Mice.

Orexin and its receptors are closely related to the pathogenesis of Alzheimer's disease (AD). Although the expression of orexin system genes under physiological condition has circadian rhythm, the diurnal characteristics of orexin system genes, and its potential role in the pathogenesis in AD are unknown. In the present study, we hope to elucidate the diurnal characteristics of orexin system genes at the early stage of AD, and to investigate its potential role in the development of AD neuropathology. We firstly detected the mRNA levels of orexin system genes, AD risk genes and core clock genes (CCGs) in hypothalamus and hippocampus in 6-month-old male 3xTg-AD mice and C57BL/6J (wild type, WT) control mice, then analyzed diurnal expression profiles of all genes using JTK_CYCLE algorithm, and did the correlation analysis between expression of orexin system genes and AD risk genes or CCGs. In addition, the expression of ß-amyloid protein (Aß) and phosphorylated tau (p-tau) protein were measured. The results showed that the diurnal mRNA expression profiles of PPO, OX1R, OX2R, Bace2, Bmal1, Per1, Per2 and Cry1 in the hypothalamus, and gene expression of OX1R, OX2R, Bace1, Bmal1, Per1 and Cry2 in the hippocampus in 3xTg-AD mice were different from that in WT mice. Furthermore, there is positive correlation between orexin system genes and AD risk genes or CCGs in the brain in 3xTg-AD mice. In addition, the expression of Aß and p-tau in hippocampus in 3xTg-AD mice were significantly increased, and the expression of p-tau is higher in night than in day. These results indicate that the abnormal expression profiles of orexin system genes and its interaction with AD risk genes or CCGs might exert important role in the pathogenesis of AD, which will increase the expression of Aß and p-tau, and accelerate the development of AD.

The associations of income and Black-White racial segregation with HIV outcomes among adults aged ≥18 years-United States and Puerto Rico, 2019.

OBJECTIVE(S): To examine associations between Index of Concentration at the Extremes (ICE) measures for economic and racial segregation and HIV outcomes in the United States (U.S.) and Puerto Rico. METHODS: County-level HIV testing data from CDC's National HIV Prevention Program Monitoring and Evaluation and census tract-level HIV diagnoses, linkage to HIV medical care, and viral suppression data from the National HIV Surveillance System were used. Three ICE measures of spatial polarization were obtained from the U.S. Census Bureau's American Community Survey: ICEincome (income segregation), ICErace (Black-White racial segregation), and ICEincome+race (Black-White racialized economic segregation). Rate ratios (RRs) for HIV diagnoses and prevalence ratios (PRs) for HIV testing, linkage to care within 1 month of diagnosis, and viral suppression within 6 months of diagnosis were estimated with 95% confidence intervals (CIs) to examine changes across ICE quintiles using the most privileged communities (Quintile 5, Q5) as the reference group. RESULTS: PRs and RRs showed a higher likelihood of testing and adverse HIV outcomes among persons residing in Q1 (least privileged) communities compared with Q5 (most privileged) across ICE measures. For HIV testing percentages and diagnosis rates, across quintiles, PRs and RRs were consistently greatest for ICErace. For linkage to care and viral suppression, PRs were consistently lower for ICEincome+race. CONCLUSIONS: We found that poor HIV outcomes and disparities were associated with income, racial, and economic segregation as measured by ICE. These ICE measures contribute to poor HIV outcomes and disparities by unfairly concentrating certain groups (i.e., Black persons) in highly segregated and deprived communities that experience a lack of access to quality, affordable health care. Expanded efforts are needed to address the social/economic barriers that impede access to HIV care among Black persons. Increased partnerships between government agencies and the private sector are needed to change policies that promote and sustain racial and income segregation.

[Research on the Progress of Applying Virtual Reality Technology in Preventing Falls in the Elderly].

The primary cause of injury and death in the elderly has been reflected in fall the elderly, so the application of reasonable and effective prevention strategies has great significance in reducing the risk of fall in the elderly. The research progress of virtual reality technology applied in preventing fall in the elderly at home and abroad over the years was systematically reviewed in this study. The mechanism of the technology in preventing fall in the elderly was mainly elaborated from five aspects of improving balance ability, gait disturbance, cognitive impairment, muscle strength and the fear psychology of falling. The purpose of this thesis is to broaden the research ideas of medical personnel on the prevention of fall of the elderly, provide more effective clinical practice plans, reduce the occurrence of fall, and guarantee the safety of the elderly.

A shape-memory poly(ε-caprolactone) hybridized TiO2/poly(l-lactide) composite with antibacterial properties.

Organic-inorganic composites as an efficient strategy to upgrade the structural and functional properties of synthetic polymers are attracting extensive attentions. However, there are few studies on the shape memory (SM) behavior of organic-inorganic composites. In the work, poly(ε-caprolactone) hybridized TiO2 nanomaterial (PCL-TiO2) is made as the switching phase and integrated into poly (l-lactide) (PLLA) to construct an SM composite. PCL-TiO2/PLLA shows "sea-island" structure and better interfacial adhesion than PCL/PLLA, which facilitates the transmission of elastic power between the switching phase and the fixing phase. PCL-TiO2 as switching phase exhibits lower enthalpy at 57 °C than PCL, and PCL-TiO2 also acts as "heat dispersion pump station", which builds a dynamically responsive system and initiates shape change. The shape fixing and recovery ratio of PCL-TiO2/PLLA are 93.9 % and 94.4 %, respectively, and go back to the original shape within 15 s at 57 °C. At the same time, PCL-TiO2 endows SMP with good antibacterial properties. Then this work provides a well-placed way for developing SM materials with structure-function integration.

A pH/enzyme dual responsive PMB spatiotemporal release hydrogel promoting chronic wound repair.

Suppressing persistent multidrug-resistant (MDR) bacterial infections and excessive inflammation is the key for treating chronic wounds. Therefore, developing a microenvironment-responsive material with good biodegradability, drug-loading, anti-infection, and anti-inflammatory properties is desired to boost the chronic wounds healing process; however, using ordinary assembly remains a defect. Herein, we propose a pH/enzyme dual-responsive polymyxin B (PMB) spatiotemporal-release hydrogel (GelMA/OSSA/PMB), namely, the amount of OSSA and PMB released from GelMA/OSSA/PMB was closely related the wound pH and the enzyme concentration changing. The GelMA/OSSA/PMB showed better biosafety than equivalent free PMB, owing to the controlled release of PMB, which helped kill planktonic bacteria and inhibit biofilm activity in vitro. In addition, the GelMA/OSSA/PMB exhibited excellent antibacterial and anti-inflammatory properties. A MDR Pseudomonas aeruginosa caused infection was effectively resolved by the GelMA/OSSA/PMB hydrogel in vivo, thereby significantly boosting wound closure during the inflammatory phase. Furthermore, GelMA/OSSA/PMB accelerated the sequential phases of wound repair.

[Mechanism of gigantol in transmembrane transport in human lens epithelial cells].

Gigantol is a phenolic component of precious Chinese medicine Dendrobii Caulis, which has many pharmacological activities such as prevent tumor and diabetic cataract. This paper aimed to investigate the molecular mechanism of gigantol in transmembrane transport in human lens epithelial cells(HLECs). Immortalized HLECs were cultured in vitro and inoculated in the laser scanning confocal microscopy(LSCM) medium at 5 000 cells/mL. The fluorescence distribution and intensity of gigantol marked by fluorescence in HLECs were observed by LSCM, and the absorption and distribution of gigantol were expressed as fluorescence intensity. The transmembrane transport process of gigantol in HLECs were monitored. The effects of time, temperature, concentration, transport inhibitors, and different cell lines on the transmembrane absorption and transport of gigantol were compared. HLECs were inoculated on climbing plates of 6-well culture plates, and the ultrastructure of HLECs was detected by atomic force microscopy(AFM) during the transmembrane absorption of non-fluorescent labeled gigantol. The results showed that the transmembrane absorption of gigantol was in time and concentration-dependent manners, which was also able to specifically target HLECs. Energy and carrier transport inhibitors reduced gigantol absorption by HLECs. During transmembrane process of gigantol, the membrane surface of HLECs became rougher and presented different degrees of pits, indicating that the transmembrane transport of gigantol was achieved by active absorption of energy and carrier-mediated endocytosis.

Emerging Prevalence and Clinical Features of Elizabethkingia meningoseptica Infection in Southwest China: A 9-Year Retrospective Study and Systematic Review.

Background: Elizabethkingia meningoseptica infections have gradually emerged as life-threatening nosocomial infections worldwide, accompanied by increasing incidence, multidrug resistance and poor outcomes. However, the epidemiology and clinical features of E. meningoseptica infection are still limited in mainland China. Methods: Patients with E. meningoseptica infections from 2011 to 2019 in southwestern China were retrospectively analyzed. The clinical features, infection patterns and outcomes were extracted from medical records and analyzed. A comprehensive systematic review was performed in accordance with PRISMA guidelines from conception to August 23, 2021. Results: Ninety-two patients were ultimately included, with the prevalence rapidly rising from 0 in 2011 to 0.19 per 1000 inpatients in 2019. A total of 93.48% of E. meningoseptica isolates were multidrug resistant, including 100% resistance to carbapenem. Furthermore, 75% of E. meningoseptica infections were concomitant with other pathogens. The mortality of our cohort was 36.96%, with risk factors for mechanical ventilation (OR=9.51, P=0.004), male sex (OR=0.27, P=0.031) and more concomitant pathogens. After propensity score matching, central venous catheters, exposure to carbapenem and antifungal drugs, and underlying tumors were associated with E. meningoseptica infection. Sixteen articles were also summarized, with reported mortality rates ranging from 11.0% to 66.6%. Blood and respiratory tract were the common sources. Piperacillin/tazobactam, trimethoprim/sulfamethoxazole, fluoroquinolone and minocycline were the most sensitive antibiotics. Inappropriate antibiotic treatment was the most commonly reported risk factor for mortality. Conclusion: Nosocomial infection with E. meningoseptica has become an emerging problem with high mortality in southwestern China. Inappropriate antibiotic treatment and central venous catheters are risk factors for infection and death and should receive adequate attention.