Low sink demand caused net photosynthetic rate decrease is closely related to the irrecoverable damage of oxygen-releasing complex and electron receptor in peach trees.

Source sink balance is one of the major determinants of carbon partitioning in plants. However, its effects on photosynthesis in fruit trees are largely unknown. In this work, the effects of low sink demand on net photosynthetic rate (Pn) and chlorophyll fluorescence after fruit removal (-fruit) in peach (Prunus persica (L.) Batsch cv. 'Zaojiubao') trees were investigated. The stepwise energy flow through photosystem II (PSII) at the reaction center (RC) was analyzed with quantitative analyses of fluorescence transient, also called JIP-test. We found that Pn was significantly lower and closely correlated to the leaf stomatal conductance (Gs) of -fruit trees than that of fruit retained (+fruit) trees. Leaf temperature (Tleaf) of -fruit trees was remarkably higher than that of +fruit trees. Day-time-period assays of chlorophyll (Chl) fluorescence revealed that, in the leaves of -fruit trees, the fluorescence parameters, such as NPQ (non-photochemical quenching coefficient) and ΦD0 (maximum quantum yield of non-photochemical de-excitation), decreased in the morning and recovered to the normal level in the afternoon, whereas other parameters, such as ΦE0 (quantum yield for electron transport at t = 0), Ψ0 (probability that a trapped exciton moves an electron to QA pool), F0 (minimum fluorescence, when all PSII RCs are open) and Wk (relative variable fluorescence at 300 µs of the chlorophyll fluorescence transient), did not. These results suggest that OEC complex and QA pool were irreversibly affected by low sink demand, whereas light harvest antenna and PSII potential efficiency retained a strong ability to recover.

The incidence of pulmonary thromboembolism in COVID-19 patients admitted to the intensive care unit: a meta-analysis and meta-regression of observational studies.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) infection is associated with a prothrombotic state. We performed a meta-analysis of proportions to estimate the weighted average incidence of pulmonary thromboembolism (PTE) in COVID-19 patients who were admitted to the intensive care unit (ICU). METHODS: We searched various medical databases for relevant studies from 31 December 2019 till 30 September 2020. We included observational studies that reported the incidence of PTE in COVID-19 patients admitted to the ICU. We extracted data related to study characteristics, patient demographics, and the incidence of PTE. Risk of bias was assessed by using the ROBINS-I tool. Statistical analysis was performed with R 3.6.3. RESULTS: We included 14 studies with a total of 1182 patients in this study. Almost all patients in this meta-analysis received at least prophylactic anticoagulation. The weighted average incidence of PTE was 11.1% (95% CI 7.7% to 15.7%, I2 = 78%, Cochran's Q test P < 0.01). We performed univariate and multivariate meta-regression, which identified the proportion of males as a significant source of heterogeneity (P = 0.03, 95% CI 0.00 to - 0.09) CONCLUSION: The weighted average incidence of PTE remains high even after prophylactic anticoagulation. PTE is a significant complication of COVID-19 especially in critically ill patients in the ICU.

Carboxylic acid-functionalized polycarbonates as bone cement additives for enhanced and sustained release of antibiotics.

Despite the good clinical outcomes of total joint replacements, prosthetic joint infections still remain a significant cause of implant failure. Primary prophylaxis is key to stemming this burgeoning problem and its associated complications. In this study, a series of bone cement formulations with enhanced antibacterial performance have been developed through the addition of carboxylic acid-functionalized polycarbonate block copolymers to commercially available bone cement. Block copolymer design features were specifically tailored to modulate the acidity for adsorption of antibiotic and phase separation of the copolymers within the polymerizing/hardening of the cement during application. The best performing polymers demonstrated sustained antimicrobial release for more than 259 days and 147 days against S. aureus and P. aeruginosa, respectively, compared to 70 days of activity seen with commercially available gentamicin-containing cement control; whilst in vitro gentamicin release was increased by 8-fold. Total porosity was also increased 3-fold from 4.3% to 12.5%, whilst maintaining the mechanical integrity, working characteristics and osteoblastic biocompatibility of bone cement. Taken together, carboxylic acid-functionalized polycarbonates represent a promising class of bone cement additives that can be used to enhance the antibacterial performance of the bone cement whilst maintaining mechanical strength and cellular biocompatibility.

A Macromolecule Reversing Antibiotic Resistance Phenotype and Repurposing Drugs as Potent Antibiotics.

In order to mitigate antibiotic resistance, a new strategy to increase antibiotic potency and reverse drug resistance is needed. Herein, the translocation mechanism of an antimicrobial guanidinium-functionalized polycarbonate is leveraged in combination with traditional antibiotics to afford a potent treatment for drug-resistant bacteria. Particularly, this polymer-antibiotic combination approach reverses rifampicin resistance phenotype in Acinetobacter baumannii demonstrating a 2.5 × 105-fold reduction in minimum inhibitory concentration (MIC) and a 4096-fold reduction in minimum bactericidal concentration (MBC). This approach also enables the repurposing of auranofin as an antibiotic against multidrug-resistant (MDR) Gram-negative bacteria with a 512-fold MIC and 128-fold MBC reduction, respectively. Finally, the in vivo efficacy of polymer-rifampicin combination is demonstrated in a MDR bacteremia mouse model. This combination approach lays foundational ground rules for a new class of antibiotic adjuvants capable of reversing drug resistance phenotype and repurposing drugs against MDR Gram-negative bacteria.

Emergency Hand and Reconstructive Microsurgery in the COVID-19-Positive Patient.

The case spectrum in hand surgery is one of extremes-purely elective day surgery cases under local anesthesia to mangling limb injuries that require immediate, and frequently, lengthy, surgery. Despite the cancellation of most elective orthopedic and plastic surgical procedures, hand surgeons around the world continue to see a steady stream of limb-threatening cases such as severe trauma and infections that require emergent surgical care. With the increase in community-spread, an increasing number of COVID-19-infected patients may be asymptomatic or have mild, nonspecific or atypical symptoms. Some of them may already have an ongoing, severe infection. The time-sensitive nature of some of these cases means that hand surgeons may need to operate urgently on patients who may be suspected of COVID-19 infections, often before confirmatory test results are available. General guidelines for perioperative care of the COVID-19-positive patient have been published. However, our practices differ from those of general orthopedic and plastic surgery, primarily because of the focus on trauma. This article discusses the perioperative and technical considerations that are essential to manage the COVID-19 patient requiring emergency care, without compromising clinical outcomes and while ensuring the safety of the attending staff.

Pandemics and Their Impact on Medical Training: Lessons From Singapore.

The ongoing coronavirus disease 2019 (COVID-19) crisis has hit Singapore hard. As of February 25, 2020, Singapore had the fourth highest number of confirmed COVID-19 infections outside of China, only trailing behind South Korea, Italy, and Japan. This has had reverberating effects on Singapore's health care system, and has, consequently, also affected medical education all the way from the undergraduate to the postgraduate level. While efforts are underway to contain disease spread and transmission, the authors believe that this is an opportune time to examine and reflect on the impact that medical crises like COVID-19 can have on medical training and education and to evaluate "business continuity plans" to ensure quality medical education even in the face of constant disruptions from pandemic outbreaks. Medical training is as important a mandate as patient care and service. The authors believe that even in trying times like this, rich and precious lessons can be sought and taught, which will immensely benefit medical students and residents-the health care leaders of tomorrow. In this Perspective, the authors discuss the various ways in which the COVID-19 crisis has affected medical instruction in Singapore and explore pertinent practical and creative solutions for the continuity of medical training in these trying times, drawing on their previous experience with the Severe Acute Respiratory Syndrome outbreak in 2003 as well as the current ongoing COVID-19 crisis.

Stromal vascular fraction promotes fibroblast migration and cellular viability in a hyperglycemic microenvironment through up-regulation of wound healing cytokines.

Diabetic wounds have impaired healing and a propensity for further morbidity, which may result in amputations. Stromal vascular fraction (SVF) is an autologous source of heterogeneous cell population obtained from adipose tissue, which is rich in stem cells and presents little immunogenicity to the host. In this study, we hypothesized that murine fibroblasts subjected to hyperglycemic conditions co-treated with SVF exhibit greater functional activity through the colorimetric MTT assay and a cell-monolayer in-vitro scratch assay. We sought to establish the underlying mechanism of action via the utility of an ELISA chemiluminescence array on the supernatant medium of the cells. Our results demonstrate that the mean percentage gap closure at 24 h in the hyperglycemia + SVF group was significantly greater at 41.1% ±â€¯1.6% compared to the hyperglycemia alone group 16.6% ±â€¯1.5% (post-hoc Bonferroni test p < 0.001, n = 3) although there was no difference between the SVF and normoglycemia group. Further, this SVF group exhibited a significantly greater 2.4 fold increase in fibroblastic cell viability as compared to the hyperglycemia alone group (p = 0.001, n = 3). The supernatant medium of the cells upon testing with ELISA indicated that early phase wound healing cytokines including platelet-derived growth factor (p = 0.012, n = 3), interleukin-1 (p = 0.003, n = 3), basic fibroblast growth factor (p = 0.003, n = 3) and interleukin-10 (p = 0.009, n = 3) were expressed in significantly greater relative luminescent units in SVF as compared to hyperglycemia alone groups (Student t-test). Taken together and for the first time, our study shows that SVF is a promising therapeutic agent for up-regulating fibroblastic activity in a hyperglycemic microenvironment, and this result can be explained in part by the stimulation of wound-healing cytokines.

A macromolecular approach to eradicate multidrug resistant bacterial infections while mitigating drug resistance onset.

Polymyxins remain the last line treatment for multidrug-resistant (MDR) infections. As polymyxins resistance emerges, there is an urgent need to develop effective antimicrobial agents capable of mitigating MDR. Here, we report biodegradable guanidinium-functionalized polycarbonates with a distinctive mechanism that does not induce drug resistance. Unlike conventional antibiotics, repeated use of the polymers does not lead to drug resistance. Transcriptomic analysis of bacteria further supports development of resistance to antibiotics but not to the macromolecules after 30 treatments. Importantly, high in vivo treatment efficacy of the macromolecules is achieved in MDR A. baumannii-, E. coli-, K. pneumoniae-, methicillin-resistant S. aureus-, cecal ligation and puncture-induced polymicrobial peritonitis, and P. aeruginosa lung infection mouse models while remaining non-toxic (e.g., therapeutic index-ED50/LD50: 1473 for A. baumannii infection). These biodegradable synthetic macromolecules have been demonstrated to have broad spectrum in vivo antimicrobial activity, and have excellent potential as systemic antimicrobials against MDR infections.

Nanomaterials in the Prevention, Diagnosis, and Treatment of Mycobacterium Tuberculosis Infections.

Despite the tremendous advancements that have been made in biomedical research, Mycobacterium tuberculosis (TB) still remains one of the top 10 causes of death worldwide, outpacing the Human Immunodeficiency Virus as a leading cause of death from an infectious disease. In the light of such significant disease burden, tremendous efforts have been made worldwide to stem this burgeoning spread of disease. The use of nanomaterials in TB management has increased in the past decade, particularly in the areas of early TB detection, prevention, and treatment. Nanomaterials have been proven to be efficacious in the rapid and accurate detection of TB pathogens. Novel nanocarriers have also shown tremendous promise in improving drug delivery, potentially enhancing drug concentrations in target organs while at the same time, reducing treatment frequency. In addition, the engineering of antigen nanocarriers represents an exciting front in TB research, potentially paving the way for the successful development of a new class of effective TB vaccines. This article discusses epidemiology and pathogenesis of TB infections, current TB therapeutics, advanced nanomaterials for anti-TB drug delivery, and TB vaccines. In addition, challenges and future perspectives in developing safe and effective nanomaterials in TB diagnosis and therapy are also presented.

Broad Spectrum Macromolecular Antimicrobials with Biofilm Disruption Capability and In Vivo Efficacy.

In this study, antimicrobial polymers are synthesized by the organocatalytic ring-opening polymerization of an eight-membered heterocyclic carbonate monomer that is subsequently quaternized with methyl iodide. These polymers demonstrate activity against clinically relevant Gram-positive Staphylococcus epidermidis and Staphylococcus aureus, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and fungus Candida albicans with fast killing kinetics. Importantly, the polymer efficiently inhibits biofilm growth and lyses existing biofilm, leading to a reduction in biomass and cell viability. In addition, the macromolecular antimicrobial is less likely to induce resistance as it acts via a membrane-lytic mechanism. The polymer is not cytotoxic toward mammalian cells with LD50 of 99.0 ± 11.6 mg kg-1 in mice through i.v. injection. In an S. aureus blood stream infection mouse model, the polymer removes bacteria from the blood more rapidly than the antibiotic Augmentin. At the effective dose, the polymer treatment does not damage liver and kidney tissues or functions. In addition, blood electrolyte balance remains unchanged after the treatment. The low cost of starting materials, ease of synthesis, nontoxicity, broad spectrum activity with fast killing kinetics, and in vivo antimicrobial activity make these macromolecular antimicrobials ideal candidates for prevention of sepsis and treatment of infections.

Highly potent antimicrobial polyionenes with rapid killing kinetics, skin biocompatibility and in vivo bactericidal activity.

Effective antimicrobial agents are important arsenals in our perennial fight against communicable diseases, hospital-acquired and surgical site multidrug-resistant infections. In this study, we devise a strategy for the development of highly efficacious and skin compatible yet inexpensive water-soluble macromolecular antimicrobial polyionenes by employing a catalyst-free, polyaddition polymerization using commercially available monomers. A series of antimicrobial polyionenes are prepared through a simple polyaddition reaction with both polymer-forming reaction and charge installation occurring simultaneously. The compositions and structures of polymers are modulated to study their effects on antimicrobial activity against a broad spectrum of pathogenic microbes. Polymers with optimized compositions have potent antimicrobial activity with low minimum inhibitory concentrations of 1.95-7.8 µg/mL and high selectivity over mammalian cells. In particular, a killing efficiency of more than 99.9% within 2 min is obtained. Moreover, the polymers demonstrate high antimicrobial efficacy against various clinically-isolated multidrug-resistant microbes, yet exhibit vastly superior skin biocompatibility in mice as compared to other clinically used surgical scrubs (chlorhexidine and betadine). Microbicidal activity of the polymer is mediated via membrane lysis as demonstrated by confocal microscopy. Unlike small molecular antibiotics, repeated use of the polymer does not induce drug resistance. More importantly, the polymer shows excellent bactericidal activity in a P. aeruginosa-contaminated mouse skin model. Given their rapid and efficacious microbicidal activity and skin compatibility, these polymers have tremendous potential to be developed as surgical scrubs/hand sanitizers to prevent multidrug-resistant infections.

Short Synthetic ß-Sheet Antimicrobial Peptides for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Burn Wound Infections.

Pseudomonas aeruginosa is often implicated in burn wound infections; its inherent drug resistance often renders these infections extremely challenging to treat. This is further compounded by the problem of emerging drug resistance and the dearth of novel antimicrobial drug discovery in recent years. In the perennial search for effective antimicrobial compounds, the authors identify short synthetic ß-sheet folding peptides, IRIKIRIK (IK8L), IRIkIrIK (IK8-2D), and irikirik (IK8D) as prime candidates owing to their high potency against Gram-negative bacteria. In this study, the peptides are first assayed against 20 clinically isolated multidrug-resistant P. aeruginosa strains in comparison with the conventional antibiotics imipenem and ceftazidime, and IK8L is demonstrated to be the most effective. IK8L also exhibits superior antibacterial killing kinetics compared to imipenem and ceftazidime. From transmission electron microscopy, confocal microscopy, and protein release analyses, IK8L shows membrane-lytic antimicrobial mechanism. Repeated use of IK8L does not induce drug resistance, while the bacteria develop resistance against the antibiotics after several times of treatment at sublethal doses. Analysis of mouse blood serum chemistry reveals that peptide does not induce systemic toxicity. The potential utility of IK8L in the in vivo treatment of P. aeruginosa-infected burn wounds is further demonstrated in a mouse model.

Construction of a high-density genetic map and QTLs mapping for sugars and acids in grape berries.

BACKGROUND: QTLs controlling individual sugars and acids (fructose, glucose, malic acid and tartaric acid) in grape berries have not yet been identified. The present study aimed to construct a high-density, high-quality genetic map of a winemaking grape cross with a complex parentage (V. vinifera × V. amurensis) × ((V. labrusca × V. riparia) × V. vinifera), using next-generation restriction site-associated DNA sequencing, and then to identify loci related to phenotypic variability over three years. RESULTS: In total, 1 826 SNP-based markers were developed. Of these, 621 markers were assembled into 19 linkage groups (LGs) for the maternal map, 696 for the paternal map, and 1 254 for the integrated map. Markers showed good linear agreement on most chromosomes between our genetic maps and the previously published V. vinifera reference sequence. However marker order was different in some chromosome regions, indicating both conservation and variation within the genome. Despite the identification of a range of QTLs controlling the traits of interest, these QTLs explained a relatively small percentage of the observed phenotypic variance. Although they exhibited a large degree of instability from year to year, QTLs were identified for all traits but tartaric acid and titratable acidity in the three years of the study; however only the QTLs for malic acid and ß ratio (tartaric acid-to-malic acid ratio) were stable in two years. QTLs related to sugars were located within ten LGs (01, 02, 03, 04, 07, 09, 11, 14, 17, 18), and those related to acids within three LGs (06, 13, 18). Overlapping QTLs in LG14 were observed for fructose, glucose and total sugar. Malic acid, total acid and ß ratio each had several QTLs in LG18, and malic acid also had a QTL in LG06. A set of 10 genes underlying these QTLs may be involved in determining the malic acid content of berries. CONCLUSION: The genetic map constructed in this study is potentially a high-density, high-quality map, which could be used for QTL detection, genome comparison, and sequence assembly. It may also serve to broaden our understanding of the grape genome.

Type 1 Bland Sutton colonic atresia complicated by fetalis hydrops in a premature neonate.

Colonic atresia (CA) is an unusual cause of neonatal intestinal obstruction where a section of the colon has failed to form, leading to blockage or absence. A premature baby was delivered at 32 weeks of gestation via caesarian section following fetal distress. She was grossly oedematous and diagnosed with severe fetalis hydrops secondary to anaemia. She was resuscitated and stabilized. On the sixth day of life, the neonate's abdomen became severely distended with billous vomiting and failure to pass meconium. We suspected intestinal obstruction and performed an omnipaque enema which revealed dilated small bowel loops and a bowel atresia. Exploratory laparotomy confirmed a Type 1 Bland Sutton CA with mucosal web. An end colostomy was successfully performed and uneventful. In our case report, we describe a rare occurrence of postnatally diagnosed CA, complicated by fetalis hydrops and anaemia.