Global antimicrobial resistance and antibiotic use in COVID-19 patients within health facilities: A systematic review and meta-analysis of aggregated participant data.

OBJECTIVES: The COVID-19 pandemic has posed a significant threat to the global healthcare system, presenting a major challenge to antimicrobial stewardship worldwide. This study aimed to provide a comprehensive and up-to-date picture of global antimicrobial resistance (AMR) and antibiotic use in COVID-19 patients. METHODS: We conducted a systematic review to determine the prevalence of AMR and antibiotic usage among COVID-19 patients receiving treatment in healthcare facilities. Our search encompassed the PubMed, Web of Science, Embase, and Scopus databases, spanning studies published from December 2019 to May 2023. We utilized random-effects meta-analysis to assess the prevalence of multidrug-resistant organisms (MDROs) and antibiotic use in COVID-19 patients, aligning with both the WHO's priority list of MDROs and the AWaRe list of antibiotic products. Estimates were stratified by region, country, and country income. Meta-regression models were established to identify predictors of MDRO prevalence and antibiotic use in COVID-19 patients. The study protocol was registered with PROSPERO (CRD 42023449396). RESULTS: Among the 11,050 studies screened, 173 were included in the review, encompassing a total of 892,312 COVID-19 patients. MDROs were observed in 42.9% (95% CI 31.1-54.5%, I2 = 99.90%) of COVID-19 patients: 41.0% (95% CI 35.5-46.6%) for carbapenem-resistant organisms (CRO), 19.9% (95% CI 13.4-27.2%) for methicillin-resistant Staphylococcus aureus (MRSA), 24.9% (95% CI 16.7-34.1%) for extended-spectrum beta-lactamase-producing organisms (ESBL), and 22.9% (95% CI 13.0-34.5%) for vancomycin-resistant Enterococcus species (VRE), respectively. Overall, 76.2% (95% CI 69.5-82.9%, I2 = 99.99%) of COVID-19 patients were treated with antibiotics: 29.6% (95% CI 26.0-33.4%) with "Watch" antibiotics, 22.4% (95% CI 18.0-26.7%) with "Reserve" antibiotics, and 16.5% (95% CI 13.3-19.7%) with "Access" antibiotics. The MDRO prevalence and antibiotic use were significantly higher in low- and middle-income countries than in high-income countries, with the lowest proportion of antibiotic use (60.1% (95% CI 52.1-68.0%)) and MDRO prevalence (29.1% (95% CI 21.8-36.4%)) in North America, the highest MDRO prevalence in the Middle East and North Africa (63.9% (95% CI 46.6-81.2%)), and the highest proportion of antibiotic use in South Asia (92.7% (95% CI 90.4-95.0%)). The meta-regression identified antibiotic use and ICU admission as a significant predictor of higher prevalence of MDROs in COVID-19 patients. CONCLUSIONS: This systematic review offers a comprehensive and current assessment of MDRO prevalence and antibiotic use among COVID-19 patients in healthcare facilities. It underscores the formidable challenge facing global efforts to prevent and control AMR amidst the backdrop of the COVID-19 pandemic. These findings serve as a crucial warning to policymakers, highlighting the urgent need to enhance antimicrobial stewardship strategies to mitigate the risks associated with future pandemics.

Impacts of pharmacist-led multifaceted antimicrobial stewardship on antibiotic use and clinical outcomes in urology department of a tertiary hospital in Guangzhou, China: an interrupted time series study.

BACKGROUND: Limited research has explored the effectiveness of pharmacist-led antimicrobial stewardship programs (ASPs) in the urology department. OBJECTIVE: To evaluate the impact of pharmacist-led multifaceted ASPs on antibiotic use and clinical outcomes. METHODS: We conducted a prescription review of inpatients receiving one or more antibiotics in the urology department of a large teaching hospital in Guangzhou, China, from April 2019 to March 2023. The pharmacist-led multifaceted ASPs intervention included guidelines development, training, medication consultation, review of medical orders, indicator monitoring, and consultation. Our primary outcome was antibiotic consumption. The data was analysed using interrupted time series (ITS) analysis. RESULTS: Following the implementation of ASPs, we observed an immediate decrease in total antibiotic consumption (ß = -32.42 DDDs/100PD and -36.24 DOT/100PD, P < 0.001), Antibiotic use rate (ß = -7.87 %, P = 0.002), Second-generation cephalosporins (ß = -12.43 DDDs/100PD and -15.18 DOT/100PD, P < 0.001), Third-generation cephalosporins (ß = -5.13 DDDs/100PD, P = 0.001 and -6.16 DOT/100PD, P = 0.002), Fluoroquinolones (ß = -12.26 DDDs/100PD and -12.70 DOT/100PD, P < 0.001), and WHO Watch category antibiotics (ß = -32.07 DDDs/100PD and -34.96 DOT/100PD, P < 0.001). There were no differences observed in mortality rate before and after the intervention, and no significant short-term or long-term effects were found on length of hospital stay (LOS) using ITS. However, there was a significant short-term effect on average antibiotic cost (ß = -446.83 RMB, P = 0.004). CONCLUSION: The implementation of pharmacist-led multifaceted ASPs had positive impacts on reducing antimicrobial consumption without increasing LOS, antibiotic cost, or mortality rate.

Is matching or discrepancy between filial piety expectation and filial support better? The role of filial support of children and social support.

Filial piety in traditional Chinese culture is an essential variable in explaining intergenerational interaction. However, previous studies have not clarified whether older adults' filial responsibility expectations matched children's filial support and the effects of the filial discrepancy on their life satisfaction and loneliness. The latent profile analysis showed that older adults were divided into two groups: (1) high expectations and support, and (2) low expectations and support. The results showed that compared with older adults with low expectations and low support, those with high expectations and high support reported higher life satisfaction and lower loneliness. Additionally, social support played a moderating role in the effect of the groups of older adults on life satisfaction and loneliness. Our conclusion shows that filial support is an essential factor influencing older adult life satisfaction and loneliness, and social support is an effective supplement to filial support.

Effect and safety of electroacupuncture on weight loss in obese patients with pre-diabetes: study protocol of a randomised controlled trial.

INTRODUCTION: Obesity has been identified as a significant risk factor for several chronic conditions, including diabetes, tumours and cardiovascular disease, and has been associated with increased mortality rates. Despite the well-established clinical practice of electroacupuncture (EA) as a potential treatment option for obesity, its efficacy remains questionable, primarily due to the paucity of empirical evidence supporting its therapeutic benefits. METHODS AND ANALYSIS: The present study aims to investigate the efficacy and safety of EA for weight loss in obese individuals with pre-diabetes, using a randomised, placebo-controlled clinical trial design. A total of 256 eligible patients will be randomly assigned to one of two groups: EA (comprising EA treatment with health education) or superficial acupuncture (SA) (comprising SA treatment with health education). The intervention will be administered three times per week for the initial 12 weeks, two times per week for the subsequent 8 weeks and one time per week for the final 4 weeks, with a 24-week follow-up period. The primary outcome measure will be the percentage of patients who achieve a reduction of 10% or more in their body weight at week 24. Secondary outcome measures will include changes in body weight and body mass index, blood test results, data collected by the body composition analyser, size of adipose tissue scanned by MRI of the abdomen and the Impact of Weight on Quality of Life, the 21-item Three-Factor Eating Questionnaire-Revised and the Food Craving Questionnaire-Trait. The Treatment Emergent Symptom Scale will be employed to monitor every adverse reaction from baseline to follow-up. ETHICS AND DISSEMINATION: This trial has received ethical clearance from the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine under the registration number 2021SHL-KY-74. All participants will provide their written informed consent prior to their enrolment. The findings of this investigation will be disseminated through peer-reviewed publications and scholarly conferences. TRIAL REGISTRATION NUMBER: NCT05237089.

A novel cholesterol metabolism-related ferroptosis pathway in hepatocellular carcinoma.

BACKGROUND: Emerging studies have reported the contribution of cholesterol to hepatocellular carcinoma (HCC) progression. However, the specific role and mechanism of cholesterol metabolism on spontaneous and progressive HCC development from the point of view of ferroptosis are still worth exploring. The present study aimed to reveal a novel mechanism of cholesterol metabolism-related ferroptosis in hepatocellular carcinoma cells. METHODS: Two microarray datasets (GSE25097, GSE22058) related to HCC were downloaded from Gene Expression Omnibus (GEO) datasets. Metabolomics analysis was performed by ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). The cholesterol-related proteins were downloaded from HMBD. Ferroptosis-related genes were extracted from FerrDb database. Data sets were separated into two groups. GSE25097 was used to identify ferroptosis-related genes, and GSE22058 was used to verify results. During these processes, chemical-protein interaction (CPI), protein-protein interaction (PPI), the Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Multivariate logistic regression analysis was used to test the associated pathway. RESULTS: We identified 8 differentially expressed ferroptosis-related genes (HAMP, PTGS2, IL1B, ALOX15B, CDKN2A, RRM2, NQO1 and KIF20A) and 4 differentially expressed cholesterol-related genes (LCAT, CH25H, CEL and CYP7A1). Furthermore, based on the predicted results with STITCH, we identified indomethacin and IL1B as the essential node for cholesterol-mediated ferroptosis in hepatocellular carcinoma cell. Multivariate logistic regression analysis showed the activities of plasma IL1B in liver cancer patients enrolled have been significantly affected by the level of plasma cholesterol (P < 0.001) and the test result of IL1B is a predictor variable causing the changes of serum Fe levels (P < 0.001). CONCLUSIONS: Our findings shed new light on the association between cholesterol metabolism and ferroptosis in HCC, and suggest that IL1B is the necessary node for cholesterol to lead to ferroptosis process in HCC. Also, we identified the potential role of indomethacin in adjuvant therapy of HCC with complications of abnormal cholesterol metabolism.

Moxibustion for medical personnel with negative emotion and insomnia during COVID-19 pandemic: A randomized, controlled trial.

Background: We conducted this randomized controlled trial (RCT) to evaluate the effectiveness and safety of moxibustion at Sanyinjiao (SP6) acupoint for treatment of negative mood and sleep quality in healthcare workers during the 2019 coronavirus disease (COVID-19). Methods: A total of 180 participants were divided in a 1:1 ratio into two groups, the treatment group (for moxibustion) and the control group (for no treatment). The treatment group had a 30-minute moxibustion therapy once a day for two weeks, followed by a two-week follow-up. The Hamilton Anxiety Scale (HAMA) was used to assess the degree of the participants' anxiety, and the Patient Health Questionnaire-9 (PHQ-9) was utilized to examine their depressed condition. The Maslach Burnout Inventory-General Survey (MBI-GS) was used to measure the level of burnout among healthcare workers. To determine the severity of insomnia, the Sleep Dysfunction Rating Scale (SDRS) was utilized. At baseline, week 2, and week 4, all scales were evaluated. Results: Compared to the control group, The treatment group improved more significantly in the HAMA at week 2 (MD = -19.01, 95% CI: -21.89 to -16.14; P<0.001) and at week 4 follow-up visits (MD = -8.96, 95% CI: -11.19 to -6.73; P<0.001). A subgroup study of HAMA scores revealed that position and education had significant impact on treatment effectiveness. During the 2-week intervention period, the treatment group showed more significant improvements in depressive symptoms measured by PHQ-9 (13.00±2.41 vs. 15.60±3.65; P<0.001), work burnout symptoms measured by MBI-GS (MD = -11.88, 95% CI, -15.73 to -8.03; P<0.001), and insomnia symptoms measured by SDRS (MD = -2.45, 95% CI, -4.24 to -0.66; P<0.01). There were no significant adverse effects reported. Conclusion: Moxibustion at SP6 may be an effective treatment to improve anxiety, depression, sleep quality, and quality of life for healthcare workers during COVID-19. Trial registration: Chinese Clinical Trial Registry (ChiCTR): ChiCTR-2200059327.

RBC Transfusion Strategy in Oncological Patients with Chronic RBC Transfusion Therapy.

BACKGROUND: Red blood cell (RBC) transfusion therapy has greatly reduced mortality and morbidity in multiply transfused patients with oncological malignancies. The aim of this study was to underline the necessity of introducing a policy for extended RBC phenotyping of these patients and for the issuing of antigen-matched blood (at least for E antigen). METHODS: Multivariate logistic regression analysis was used to evaluate the associations of age, gender, transfusion history, and various malignancies with the development of red cell alloimmunization. RESULTS: Given the results of antibody identification, we finally obtained 732 cases to be analyzed, designating them as the p group. The respiratory system (231/732; 31.6%), digestive system (273/732; 37.3%), and female reproductive system (127/732; 17.3%) had the three highest alloimmunization rates in the p group. We screened 81 cases from the p group for which antibody screening in our laboratory had historically yielded negative results. Among the 81 cases with antibody seroconversion, anti-E was the most frequently observed antibody (37%). CONCLUSIONS: The results related to multivariate logistic regression analysis of the Rh group indicate that, in contrast to the other variates, transfusion confers a strongly increased risk of Rh blood system-related red cell alloimmunization. To reduce alloimmunization in tumor patients, it will be essential to introduce a policy for extended RBC phenotyping of high-risk patients and for the issuing of antigen-matched blood (at least for E antigen).

PatU3 plays a central role in coordinating cell division and differentiation in pattern formation of filamentous cyanobacterium Nostoc sp. PCC 7120.

Spatial periodic signal for cell differentiation in some multicellular organisms is generated according to Turing's principle for pattern formation. How a dividing cell responds to the signal of differentiation is addressed with the filamentous cyanobacterium Nostoc sp. PCC 7120, which forms the patterned distribution of heterocysts. We show that differentiation of a dividing cell was delayed until its division was completed and only one daughter cell became heterocyst. A mutant of patU3, which encodes an inhibitor of heterocyst formation, showed no such delay and formed heterocyst pairs from the daughter cells of cell division or dumbbell-shaped heterocysts from the cells undergoing cytokinesis. The patA mutant, which forms heterocysts only at the filament ends, restored intercalary heterocysts by a single nucleotide mutation of patU3, and double mutants of patU3/patA and patU3/hetF had the phenotypes of the patU3 mutant. We provide evidence that HetF, which can degrade PatU3, is recruited to cell divisome through its C-terminal domain. A HetF mutant with its N-terminal peptidase domain but lacking the C-terminal domain could not prevent the formation of heterocyst pairs, suggesting that the divisome recruitment of HetF is needed to sequester HetF for the delay of differentiation in dividing cells. Our study demonstrates that PatU3 plays a key role in cell-division coupled control of differentiation.

Benefits of exercise training on divergent thinking: The mediating role of ambiguity tolerance.

Exercise training has been proposed as a method for improving cognitive function. However, it is unknown whether chronic physical activity promotes divergent thinking and its underlying mechanism. Ambiguity tolerance has been considered relevant to divergent thinking. Therefore, this study sought to investigate whether individuals engaging in different types of exercise training differed in divergent thinking and to examine the mediating role of ambiguity tolerance underlying the training effect. The study was conducted in a sample of 492 university students who completed the unusual use task and the ambiguity tolerance questionnaire. The results revealed that individuals who underwent physical training proposed more creative ideas than non-physical training individuals did. Individuals engaging in multiple movement training scored higher in fluency, flexibility, and originality than their counterparts engaging in single movement training. Furthermore, ambiguity tolerance fully explained the difference in divergent thinking fluency between the physical and non-physical training groups. These findings provide preliminary evidence for the benefits of physical training on divergent thinking.

Do daily interaction patterns differ between empty nesters and non-empty nesters? The role of different interaction partners in a Chinese sample.

The empty nest is a phase of life that most parents will experience when their children grow up and leave home. However, little attention has been given to changes that take place in empty nesters' daily patterns of interaction. This study aimed to examine the differences between empty nesters and non-empty nesters in relation to their daily interactions and the affect of various social partners. A total of 208 participants were recruited via convenience sampling; they were asked to record their daily interactions using the Rochester Interaction Record and to rate their affect after each interaction using the Positive Affect-Negative Affect Scale. The results showed that daily interactions were related to a higher increase of positive affect in empty nesters than in non-empty nesters when interactions were with adult children. In contrast, daily interactions of non-empty nesters were related to a higher decrease in negative affect when the interactions were with friends, neighbors, and strangers. These findings indicate that the patterns of daily interactions differ between empty nesters and non-empty nesters. Specifically, the daily interactions of empty nesters were seen to be more related to a higher increase in positive affect, whereas the daily interactions of non-empty nesters were seen to be more related to a higher decrease in negative affect. This study showed the differences in daily interaction patterns between empty and non-empty nesters across diverse social partners. The findings on the daily interaction patterns have some implications for older adults: (1) empty nesters can improve daily interaction with adult children, relatives, and colleagues for a higher positive affect; (2) non-empty nesters can improve daily interactions with friends, neighbors, and strangers to relieve their negative affect.

High-Throughput Peptide Arrays Identify Potential Diagnostic Autoantibody Signatures in Early-Stage Lung Adenocarcinoma.

BACKGROUND: Early diagnosis is critical to lung adenocarcinoma patients' survival but faces inadequacies in convenient early detection. METHODS: We applied a comprehensive microarray of 130,000 peptides to detect "autoantibody signature" that is autoantibodies binding to mimotopes for early detection of stage 0-I LUAD. Plasma samples were collected from 147 early-stage lung adenocarcinoma (Early-LUAD), 108 benign lung disease (BLD), and 122 normal healthy controls (NHC). Clinical characteristics, low-dose CT (LDCT), and laboratory tests were incorporated into correlation analysis. RESULTS: We identified 143 and 133 autoantibody signatures, distinguishing Early-LUAD from NHC/BLD in the discovery cohort. Autoantibody signatures significantly correlated with age, stage, tumor size, basophil count, and IgM level (P < 0.05). The random forest models based on differential autoantibody signatures displayed AUC of 0.92 and 0.87 to discern Early-LUAD from NHC/BLD in the validation cohort, respectively. Compared with LDCT, combining autoantibody signature and LDCT improved the positive predictive value from 50% to 78.33% (P = 0.049). In addition, autoantibody signatures displayed higher sensitivity of 72.4% to 81.0% compared with the combinational tumor markers (cyfra21.1, NSE, SCC, ProGRP) with a sensitivity of 22.4% (P = 0.000). Proteins matched by differential peptides were enriched in cancer-related PI3K/Akt, MAPK, and Wnt pathways. Overlaps between matched epitopes and autoantibody signatures illustrated the underlying engagement of autoantibodies in immune recognition. CONCLUSIONS: Collectively, autoantibody signatures identified by a high-throughput peptide microarray have the potential to detect Early-LUAD, which could assist LDCT to better diagnose Early-LUAD. IMPACT: Novel sensitive autoantibody signatures can adjuvant LDCT to better diagnose LUAD at very early stage.

Multiple configuration transitions of soft actuators under single external stimulus.

Soft actuators have a wide range of applications in medical instruments, soft robotics, 3D electronics, and deployable structures, where configuration transitions are crucial for their function realization. However, most soft actuators can only morph from the initial configuration directly to the final configuration under a single external stimulus. Herein, we report a novel soft actuator by 3D printing parallel strips with crescent cross-sections onto a thin PDMS film. Multiple configuration transitions are observed when the soft actuator swells in ethyl acetate. Four factors, i.e., the geometric asymmetry of the strips, the fabrication-induced heterogeneity of the film, the differential swelling ratios of the strips and the film, and the geometric parameters of the actuator, are demonstrated to synergistically regulate the multiple configuration transitions of the actuator. Particularly, the underlying mechanisms for the configuration transitions are systematically investigated through experiments and theoretical analysis, and verified via finite element simulation. Benefitting from the multiple configuration transitions, the grasp-release-re-grab function of the actuator is demonstrated under a single stimulus. This work contributes to fundamental understanding of the morphing behaviors and the novel design of soft actuators.

Collagen characteristics affect the texture of pork Longissimus and Biceps femoris.

Connective tissue is considered to influence the toughness of pork, but most studies on connective tissue focus on the loin muscle. Cooking loss, Warner-Bratzler shear force (WBSF), texture profile analysis (hardness, springiness, chewiness, resilience, and cohesiveness), total and insoluble collagen content, the percentage of type III collagen relative to the total of type I and III collagen, proteoglycan content and intramuscular fat (IMF) content were measured for pork Biceps femoris (BF) and Longissimus thoracis et lumborum (LTL) and Pearson's correlation was performed. The results showed that BF had higher WBSF, resilience, total, and insoluble collagen content than LTL (P < 0.05). When considering both muscles, total and insoluble collagen content were positively correlated (P < 0.05) with WBSF (r = 0.47 and 0.49, respectively), hardness (r = 0.49 and 0.50, respectively), cohesiveness (r = 0.50 and 0.50, respectively), chewiness (r = 0.58 and 0.59, respectively) and resilience (r = 0.63 and 0.63, respectively). The percentage of type III collagen content was negatively correlated (P < 0.05) with WBSF (r = -0.68) and hardness (r = -0.58). Collagen content was correlated (P < 0.05) with WBSF (r = 0.75) and hardness (r = 0.61) in LTL and with cohesiveness (r = 0.74) and resilience (r = 0.63) in BF. Collagen characteristics differ between muscles and contribute to pork texture in both LTL and BF.

Fatal heart disease in patients with bone and soft tissue sarcoma.

Background/purpose: With improved cancer survivorship, non-cancer events, especially heart disease (HD), have become the underlying cause of death in cancer patients, but the risk of HD mortality in sarcoma patients remains poorly characterized. Therefore, our purpose was to: (1) identify sarcoma patients at the highest risk of fatal HD compared with the general population, (2) identify patients and sarcoma characteristics associated with a higher risk of HD death, and (3) determine if chemotherapy increased the risk of HD death in sarcoma patients. Methods: From 1975 to 2016, we identified patients diagnosed with bone and soft tissue sarcoma from the Surveillance, Epidemiology, and End Results (SEER) database in the US. Standardized mortality ratios (SMRs) were evaluated using mortality data from the general population collected by the National Center for Health Statistics. This was the largest retrospective cohort study of fatal HD in individuals with sarcoma. Results: In 80,905 sarcoma patients observed for 530,290 person-years, 3,350 deaths from HD were identified with a mortality of 631.7/100,000 person-years. The SMR of death from HD was 1.38 (95% CI: 1.33-1.42). The highest risks of death from HD were observed in patients with Ewing sarcoma (SMR = 5.44; 95% CI: 3.38-8.75) and osteosarcoma (SMR = 1.92; 95% CI: 1.55-2.38). Patients diagnosed at < 19 years old had the highest SMR in all age subgroups, and a higher risk of fatal HD relative to the general population was observed in sarcoma survivors diagnosed at < 85 years old. In patients diagnosed at < 19 years old, HD plurality occurred in those with Ewing sarcoma (29.4%) and osteosarcoma (32.4%) and at > 35 years old, HD plurality occurred in those diagnosed with liposarcoma (19.0%) and malignant fibro histiocytoma (MFH) (23.6%). For sarcoma survivors, HD mortality risks were highest within the first year after diagnosis (SMR = 1.31; 95% CI: 1.21-1.41), and this risk remained elevated throughout follow-up compared with the general population. Subgroup analyses indicated that chemotherapy significantly increased the risk of fatal HD in patients with localized osteosarcoma (Hazard ratio (HR) = 3.18; 95% CI: 1.24-8.13; P = 0.016), but not in patients with other histological sarcoma subtypes and clinical stages. Conclusion: The risk of death from HD mainly varied in patients with different histological sarcoma subtypes and clinical stages. Chemotherapy increased the risk of fatal HD in patients with localized osteosarcoma. To lower the risk of fatal HD in patients with sarcoma, we call for enhanced multidisciplinary cooperation, including cardiologists and orthopedic surgeons.

Attachment of Ferredoxin: NADP+ Oxidoreductase to Phycobilisomes Is Required for Photoheterotrophic Growth of the Cyanobacterium Synechococcus sp. PCC 7002.

Two types of cyanobacterial phycobilisomes (PBS) are present: the hemidiscoidal PBS (CpcG-PBS) and the membrane-bound PBS (CpcL-PBS). Both types of PBS have ferredoxin:NADP+ oxidoreductase (FNR) attached to the termini of their rods through a CpcD domain. To date, the physiological significance of the attachment remains unknown. We constructed a mutant (dF338) which contains an FNR lacking the N-terminal CpcD domain in Synechococcus sp. PCC 7002. Isolated CpcG-PBS from dF338 did not contain FNR and the cell extracts of the mutant had a 35 kDa protein cross-reacting to anti-FNR antibodies. dF338 grows normally under photoautotrophic conditions, but little growth was observed under photoheterotrophic conditions. A cpcL (cpcG2) mutant grows extremely slowly under photoheterotrophic conditions while a cpcG (cpcG1) mutant, in which PBS rods could not attach to the cores of the CpcG-PBS, can grow photoheterotrophically, strongly suggesting that the attachment of FNR to CpcL-PBS is critical to photoheterotrophic growth. We show that electron transfer to the plastoquinone pool in dF338 and the cpcL mutant was impaired. We also provide evidence that trimeric photosystem I (PSI) and intact CpcL-PBS with a full-length FNR is critical to plastoquinone reduction. The presence of a NADPH-dehydrogenase (NDH)-CpcL-PBS-PSI trimer supercomplex and its roles are discussed.

Acellular dermal matrix decorated with collagen-affinity peptide accelerate diabetic wound healing through sustained releasing Histatin-1 mediated promotion of angiogenesis.

Treating diabetic ulcers is a major challenge in clinical practice, persecuting millions of patients with diabetes and increasing the medical burden. Recombinant growth factor application can accelerate diabetic wound healing via angiogenesis. The local administration of recombinant growth factors has no robust clinical efficiency because of the degradation of append short duration of the molecules in the hostile inflammatoryenvironment.The present study focused on the pathophysiology of impaired neovascularization and growth factor short duration in the diabetic wound. We prepared a collagen-binding domain (CBD)-fused recombinant peptide (C-Histatin-1) that had both pro-angiogenesis capacity and collagen-affinity properties. Next, we created a biocompatible acellular dermal matrix (ADM) as a drug delivery carrier that featured collagen-richness, high porosity, and non-cytotoxicity. C-Histatin-1 was then tethered on ADM to obtain a sustained-release effect. Finally, a functional scaffold (C-Hst1/ADM) was developed. C-Hst1/ADM can sustain-release Histatin-1 to promote the adhesion, migration, and angiogenesisof vascular endothelial cells in vitro. Using a diabetic wound model, we showed that C-Hst1/ADM could significantly promote angiogenesis, reduce scar widths, and improve extracellular collagen accumulation. Therefore, the results of this study provide a foundation for the clinical application of C-Hst1/ADM covering scaffold in the treatment of diabetic wounds.

Physically Entangled Antiswelling Hydrogels with High Stiffness.

Physically cross-linked hydrogels have great potential for tissue engineering because of their excellent biocompatibility and easy fabrication. However, physical cross-linking points are typically weaker compared to chemical ones and therefore cannot form robust hydrogels with excellent water stability, which greatly hinder their further applications. In this work, a novel hydrogel with high stiffness and outstanding antiswelling performance cross-linked by hydrophobic polymer chains entanglements is reported. The hydrophobic polymer polyimide (PI) is mixed with the hydrophilic polymer poly-(vinyl pyrrolidone) (PVP) to form cross-linking points between the chains. At the equilibrium swelling state, tensile modulus of the hydrogel can be up to 22.57 MPa (higher than most existing hydrogels) and the equilibrium water swelling ratio (ESR) can be as low as 125.0%. By decreasing the PI mass ratio, tensile modulus and ESR of the hydrogel can be tuned in a wide range from 22.57 to 0.005 MPa and 125.0% to 765.6%, respectively. Using PVP/PI solutions as inks, uniform structures and multi-material structures are fabricated having mechanical properties close to cartilage through a direct ink writing 3D printing platform. This current work demonstrates that entangled PVP/PI hydrogels have excellent tailoring capabilities and are promising candidates for tissue engineering applications.