The impact of heterotopic ovarian tissue transplantation with varied volumes on reproductive endocrine function in oophorectomized rats.

BACKGROUND: This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function of rats after oophorectomy. METHODS: Female rats were selected to establish a castration model and then underwent different volumes of ovarian tissue transplantation. Group I served as the sham operation group. The transplantation group was divided into five subgroups based on the calculated ratio of ovarian weight to body weight in normal female rats, δ = (2.52 ± 0.17) ×10-4: Group II: transplanted ovarian volume was δ; Group III: 0.75δ; Group IV: 0.5δ; Group V: 0.25δ; Group VI: without ovarian transplantation. The post-transplant oestrous cycle recovery was observed, and blood samples were collected every 2 weeks to measure serum hormone levels. Histological evaluation was performed at the end of the observation period. RESULTS: Rats in Group V exhibited disrupted oestrous cycles after transplantation, which were significantly longer than those in Group I. Rats in Groups II, III, and IV showed no cyclic changes. At 6 weeks post-transplantation, rats in Group V had lower E2 and AMH levels and higher FSH levels compared to Group I. The uterine wet weight and the number of normal follicles in Group V were significantly lower than those in Group I, but the number of atretic follicles was higher than in Group I. CONCLUSION: The larger ovarian tissue transplantation resulted in a faster recovery with a higher survival rate of the uterus and normal follicles, compared to smaller ovarian tissue transplantation.

With advancements in science and technology, ovarian transplantation techniques have become increasingly mature. However, there are still many questions that need to be addressed. For instance, the large size of the transplanted ovarian tissues may cause over-recruitment of the primordial follicles. When the transplanted ovarian tissue is too small, it can only exert limited functionality and may not meet the patient's needs. This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function in rats after oophorectomy, and to provide a theoretical basis for determining the minimum effective volume of heterotopic ovarian tissue transplantation.

Dosimetric analysis of brachial plexopathy after stereotactic body radiotherapy: Significance of organ delineation.

OBJECTIVES: Examine the significance of contouring the brachial plexus (BP) for toxicity estimation and select metrics for predicting radiation-induced brachial plexopathy (RIBP) after stereotactic body radiotherapy. MATERIALS AND METHODS: Patients with planning target volume (PTV) ≤ 2 cm from the BP were eligible. The BP was contoured primarily according to the RTOG 1106 atlas, while subclavian-axillary veins (SAV) were contoured according to RTOG 0236. Apical PTVs were classified as anterior (PTV-A) or posterior (PTV-B) PTVs. Variables predicting grade 2 or higher RIBP (RIBP2) were selected through least absolute shrinkage and selection operator regression and logistic regression. RESULTS: Among 137 patients with 140 BPs (median follow-up, 32.1 months), 11 experienced RIBP2. For patients with RIBP2, the maximum physical dose to the BP (BP-Dmax) was 46.5 Gy (median; range, 35.7 to 60.7 Gy). Of these patients, 54.5 % (6/11) satisfied the RTOG limits when using SAV delineation; among them, 83.3 % (5/6) had PTV-B. For patients with PTV-B, the maximum physical dose to SAV (SAV-Dmax) was 11.2 Gy (median) lower than BP-Dmax. Maximum and 0.3 cc biologically effective doses to the BP based on the linear-quadratic-linear model (BP-BEDmax LQL and BP-BED0.3cc LQL, α/ß = 3) were selected as predictive variables with thresholds of 118 and 73 Gy, respectively. CONCLUSION: Contouring SAV may significantly underestimate the RIBP2 risk in dosimetry, especially for patients with PTV-B. BP contouring indicated BP-BED0.3cc LQL and BP-BEDmax LQL as potential predictors of RIBP2.

Stem Cell Therapy in Neonatal Hypoxic-Ischemic Encephalopathy and Cerebral Palsy: a Bibliometric Analysis and New Strategy.

The aim of this study was to identify related scientific outputs and emerging topics of stem cells in neonatal hypoxic-ischemic encephalopathy (NHIE) and cerebral palsy (CP) through bibliometrics and literature review. All relevant publications on stem cell therapy for NHIE and CP were screened from websites and analyzed research trends. VOSviewer and CiteSpace were applied to visualize and quantitatively analyze the published literature to provide objective presentation and prediction. In addition, the clinical trials, published articles, and projects of the National Natural Science Foundation of China associated with stem cell therapy for NHIE and CP were summarized. A total of 294 publications were associated with stem cell therapy for NHIE and CP. Most publications and citations came from the USA and China. Monash University and University Medical Center Utrecht produced the most publications. Pediatric research published the most studies on stem cell therapy for NHIE and CP. Heijnen C and Kavelaars A published the most articles. Cluster analyses show that current research trend is more inclined toward the repair mechanism and clinical translation of stem cell therapy for NHIE and CP. By summarizing various studies of stem cells in NHIE and CP, it is indicated that this research direction is a hot topic at present. Furthermore, organoid transplantation, as an emerging and new therapeutic approach, brings new hope for the treatment of NHIE and CP. This study comprehensively summarized and analyzed the research trend of global stem cell therapy for NHIE and CP. It has shown a marked increase in stem cell therapy for NHIE and CP research. In the future, more efforts will be made on exploring stem cell or organoid therapy for NHIE and CP and more valuable related mechanisms of action to achieve clinical translation as soon as possible.

Auto-setting multi-soliton temporal spacing in a fiber laser by a hybrid GA-PSO algorithm.

Multi-soliton operation in fiber lasers is a promising platform for the investigation of soliton interaction dynamics and high repetition-rate pulse. However, owing to the complex interaction process, precisely manipulating the temporal spacing of multiple solitons in a fiber laser is still challenging. Herein, we propose an automatic way to control the temporal spacing of multi-soliton operation in an ultrafast fiber laser by a hybrid genetic algorithm-particle swarm optimization (GA-PSO) algorithm. Relying on the intelligent adjustment of the electronic polarization controller (EPC), the on-demand temporal spacing of the double solitons can be effectively achieved. In particular, the harmonic mode locking with equal temporal spacing of double solitons is also obtained. Our approach provides a promising way to explore nonlinear soliton dynamics in optical systems and optimize the performance of ultrafast fiber lasers.

Design of Four Small-Molecule-Inducible Systems in the Yeast Chromosome, Applied to Optimize Terpene Biosynthesis.

The optimization of cellular functions often requires the balancing of gene expression, but the physical construction and screening of alternative designs are costly and time-consuming. Here, we construct a strain of Saccharomyces cerevisiae that contains a "sensor array" containing bacterial regulators that respond to four small-molecule inducers (vanillic acid, xylose, aTc, IPTG). Four promoters can be independently controlled with low background and a 40- to 5000-fold dynamic range. These systems can be used to study the impact of changing the level and timing of gene expression without requiring the construction of multiple strains. We apply this approach to the optimization of a four-gene heterologous pathway to the terpene linalool, which is a flavor and precursor to energetic materials. Using this approach, we identify bottlenecks in the metabolic pathway. This work can aid the rapid automated strain development of yeasts for the bio-manufacturing of diverse products, including chemicals, materials, fuels, and food ingredients.

Critical Role of Monooxygenase in Biodegradation of 2,4,6-Trinitrotoluene by Buttiauxella sp. S19-1.

2,4,6-Trinitrotoluene (TNT) is an aromatic pollutant that is difficult to be degraded in the natural environment. The screening of efficient degrading bacteria for bioremediation of TNT has received much attention from scholars. In this paper, transcriptome analysis of the efficient degrading bacterium Buttiauxella sp. S19-1 revealed that the monooxygenase gene (BuMO) was significantly up-regulated during TNT degradation. S-ΔMO (absence of BuMO gene in S19-1 mutant) degraded TNT 1.66-fold less efficiently than strain S19-1 (from 71.2% to 42.9%), and E-MO mutant (Escherichia coli BuMO-expressing strain) increased the efficiency of TNT degradation 1.33-fold (from 52.1% to 69.5%) for 9 h at 180 rpm at 27 °C in LB medium with 1.4 µg·mL-1 TNT. We predicted the structure of BuMO and purified recombinant BuMO (rBuMO). Its specific activity was 1.81 µmol·min-1·mg-1 protein at pH 7.5 and 35 °C. The results of gas chromatography mass spectrometry (GC-MS) analysis indicated that 4-amino-2,6-dinitrotoluene (ADNT) is a metabolite of TNT biodegradation. We speculate that MO is involved in catalysis in the bacterial degradation pathway of TNT in TNT-polluted environment.

OsCSN1 regulates the growth of rice seedlings through the GA signaling pathway in blue light.

Blue light can regulate the photomorphogenesis of plants through blue light receptors to influence seedling growth and development. The COP9 signaling complex (CSN), a vital regulator of photomorphogenesis, is a highly conserved protein complex. CSN1 is the largest and most critical subunit in the CSN with a complex N-terminal function that supports most of the functions of CSN1 and is mainly involved in plant growth and development processes. The CSN is also required in the blue light-mediated photomorphogenesis response of seedlings. In this study, the OsCSN1 subunit of Oryza sativa subsp. japonica (rice) was edited and screened, and OsCSN1 deletion mutant, OsCSN1 weak expression mutant and OsCSN1 overexpression mutant were constructed. The mechanism of OsCSN1 and its N-terminal effects on rice seedling growth and development under blue light conditions were investigated. The addition of exogenous hormone gibberellin (GA3) and gibberellin synthesis inhibitor paclobutrazol (PAC) caused aboveground phenotypic and protein (such as CUL4 and SLR1) changes. Blue light regulates the degradation of SLR1 through OsCSN1, which regulates the growth and development of rice seedling height, the first incomplete leaf, and the coleoptile. It is hypothesized that rice affects CRY-COP1 interactions after sensing blue light signals through the cryptochrome, and the nuclear localization of COP1 is regulated by the CSN complex. OsCSN1 is a negative regulator in response to blue light. The core structural domain of action that inhibits the growth of the aboveground part of rice seedlings is located at the N-terminal of OsCSN1. OsCSN1 regulates the nuclear localization of COP1 through the COP9 signaling complex and degrades SLR1 through CUL4-based E3 ligase. Ultimately, it affects the synthesis of the endogenous hormone GA, thereby inhibiting the aboveground growth and development of rice seedlings.

MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters.

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products. MIBiG 3.0 is accessible online at https://mibig.secondarymetabolites.org/.

Secondary Metabolites of Osmanthus fragrans: Metabolism and Medicinal Value.

Osmanthus fragrans (scientific name: Osmanthus fragrans (Thunb.) Lour.) is a species of the Osmanthus genus in the family Oleaceae, and it has a long history of cultivation in China. O. fragrans is edible and is well known for conferring a natural fragrance to desserts. This flowering plant has long been cultivated for ornamental purposes. Most contemporary literature related to O. fragrans focuses on its edible value and new species discovery, but the functional use of O. fragrans is often neglected. O, fragrans has many properties that are beneficial to human health, and its roots, stems, leaves, flowers and fruits have medicinal value. These characteristics are recorded in the classics of traditional Chinese medicine. Studies on the metabolites and medicinal value of O. fragrans published in recent years were used in this study to evaluate the medicinal value of O. fragrans. Using keywords such as metabolites and Osmanthus fragrans, a systematic and nonexhaustive search of articles, papers and books related to the medicinal use of Osmanthus fragrans metabolites was conducted. Fifteen metabolites were identified through this literature search and classified into three categories according to their properties and structure: flavonoids, terpenes and phenolic acids. It was found that the pharmacological activities of these secondary metabolites mainly include antioxidant, anticancer, anti-inflammatory and antibacterial activities and that these metabolites can be used to treat many human diseases, such as cancer, skin diseases, cardiovascular diseases, and neurological diseases. Most of the reports that are currently available and concern the secondary metabolites of Osmanthus fragrans have limitations. Some reports introduce only the general classification of compounds in Osmanthus fragrans, and some reports introduce only a single compound. In contrast, the introduction section of this paper includes both the category and the functional value of each compound. While reviewing the data for this study, the authors found that the specific action sites of these compounds and their mechanisms of action in plants are relatively weak, and in the future, additional research should be conducted to investigate this topic further.

Recent Advances in Metal-Based Nanoparticle-Mediated Biological Effects in Arabidopsis thaliana: A Mini Review.

The widespread application of metal-based nanoparticles (MNPs) has prompted great interest in nano-biosafety. Consequently, as more and more MNPs are released into the environment and eventually sink into the soil, plants, as an essential component of the ecosystem, are at greater risk of exposure and response to these MNPs. Therefore, to understand the potential impact of nanoparticles on the environment, their effects should be thoroughly investigated. Arabidopsis (Arabidopsis thaliana L.) is an ideal model plant for studying the impact of environmental stress on plants' growth and development because the ways in which Arabidopsis adapt to these stresses resemble those of many plants, and therefore, conclusions obtained from these scientific studies have often been used as the universal reference for other plants. This study reviewed the main findings of present-day interactions between MNPs and Arabidopsis thaliana from plant internalization to phytotoxic effects to reveal the mechanisms by which nanomaterials affect plant growth and development. We also analyzed the remaining unsolved problems in this field and provide a perspective for future research directions.

Effects of therapeutic hypothermia on the safety of children with severe traumatic brain injury: a systematic review and meta-analysis.

Background: Therapeutic hypothermia (TH) is effective to treat adult traumatic brain injury (TBI), but there is still controversy about its safety to treat the children with severe TBI. Methods: Clinical studies on TH in children with severe TBI from January 2000 to September 2020 were screened in PubMed, Web of Science, Embase, Cochrane Library, Nature, NCKI, and Wanfang online databases. Data were meta-analyzed by Rev Man 5.3. Differences in mortality, adverse outcomes, duration of Pediatric Intensive Care Unit (PICU), incidence of infection, and incidence of arrhythmia were compared between experimental group and control group. The heterogeneity of the results was evaluated by chi-square test and I2 test in Rev Man 5.3, and publication bias was evaluated by funnel plot. Results: Five articles were included, including 421 children. Cochrane evaluation was B grade or above, and Jadad scale score was over three points. The overall mortality between two groups showed great difference [odds ratio (OR) =1.72, 95% CI: 0.98-3.02, Z=1.87, P=0.04]. The incidence of adverse outcomes (OR =1.39, 95% CI: 0.86-2.25, Z=1.34, P=0.18), the duration of PICU [mean difference (MD) =0.51, 95% CI: -0.33 to 1.35, Z=1.19, P=0.24], the incidence of infection (OR =0.79, 95% CI: 0.51-1.23, Z=1.03, P=0.30), and the incidence of arrhythmia (OR =3.10, 95% CI: 0.77-12.50, Z=1.59, P=0.11) were not considerably different. Discussion: TH significantly reduced overall mortality in children with severe TBI, but did not significantly improve the incidence of adverse outcomes, PICU duration, infection rate, or arrhythmia. These results provided a reference for selecting proper clinical treatment methods for children with severe TBI.

Surfactant-Free Green Synthesis of Au@Chlorophyll Nanorods for NIR PDT-Elicited CDT in Bladder Cancer Therapy.

The facile and straightforward fabrication of NIR-responsive theranostic materials with high biocompatibility is still an unmet need for nanomedicine applications. Here, we used a natural photosensitizer, iron chlorophyll (Chl/Fe), for the J-aggregate template-assisted synthesis of Au@Chl/Fe nanorods with high stability. The assembly of a high amount of Chl/Fe J-aggregate onto the Au surface enabled red-NIR fluorescence for monitoring and tracking residential tumor lesions. The Chl/Fe moieties condensed on the nanorods could change the redox balance by the photon induction of reactive oxygen species and attenuate iron-mediated lipid peroxidation by inducing a Fenton-like reaction. After conjugation with carboxyphenylboronic acid (CPBA) to target the glycoprotein receptor on T24 bladder cancer (BC) cells, the enhanced delivery of Au@Chl/Fe-CPBA nanorods could induce over 85% cell death at extremely low concentrations of 0.16 ppm[Au] at 660 nm and 1.6 ppm[Au] at 785 nm. High lipid peroxidation, as shown by BODIPY staining and GSH depletion, was observed when treated T24 cells were exposed to laser irradiation, suggesting that preliminary photodynamic therapy (PDT) can revitalize Fenton-like reaction-mediated chemodynamic ferroptosis in T24 cells. We also manipulated the localized administration of Au@Chl-Fe combined with PDT at restricted regions in orthotopic tumor-bearing mice to cure malignant BC successfully without recurrence. By intravesical instillation of the Au@Chl/Fe-CPBA nanorods, this localized treatment could prevent the material from entering the systemic circulation, thus minimizing systemic toxicity. Upon activating NIR-PDT-elicited chemodynamic therapy, ultrasound imaging revealed almost complete tumor remission. Anti-tumor efficacy and survival benefit were achieved with a green photosensitizer.

Synthesis, Structural Characterization, and Water Vapor Sorption Behavior of Two Ligand Ratio-Dependent Supramolecular Networks, [Cd(2,2'-bpym)1.5(BDC)]·0.5(2,2'-bpym)·5H2O and [Cd(2,2'-bpym)0.5(BDC)(H2O)3].

Two ligand ratio-dependent supramolecular networks, [Cd(2,2'-bpym)1.5(BDC)]·0.5(2,2'-bpym)·5H2O (1) and [Cd(2,2'-bpym)0.5(BDC)(H2O)3] (2), (BDC2- = dianion of terephthalic acid and 2,2'-bpym = 2,2'-bipyrimidine) have been synthesized and structurally characterized by the single-crystal X-ray diffraction method. Structural determination reveals that compound 1 is a two-dimensional (2D) layered metal-organic framework (MOF) constructed via the bridges of Cd(II) ions with 2,2'-bpym and BDC2- ligands, and compound 2 is a zero-dimensional (0D) 2,2'-bpym-bridged di-Cd(II) monomeric complex. When the thermally dehydrated powders of 1 (at 100 °C) were immersed into water solution, most of the dehydrated powders of 1 underwent structural transformation back to rehydrated 1, but very little amounts of the dehydrated powders of 1 were decomposed to light-brown crystals of 2 or colorless crystals of a new coordination polymer (CP), [Cd(2,2'-bpym)(BDC)(H2O)]·3H2O (3), with its one-dimensional (1D) zigzag chain-like framework being constructed via the bridges of Cd(II) ions with the BDC2- ligand. Structural analysis reveals that all 3D supramolecular networks of 1-3 are further constructed via strong intermolecular interactions, including hydrogen bonds and π-π stacking interactions. Compounds 1 and 2 both exhibit significant water vapor hysteresis isotherms, and their cyclic water de-/adsorption behavior accompanied with solid-state structural transformation has been verified by de-/rehydration TG analyses and powder X-ray diffraction (PXRD) measurements.

Differences between cultured cortical neurons by trypsin and papain digestion.

The objective of this study was to compare the efficiency of trypsin and papain in neuronal digestion and determine which enzyme is more efficient. Cortical tissues were obtained from Sprague-Dawley (SD) rats. According to the different digestive enzymes, the samples were divided into the trypsin group and the papain group. After being digested by each of the two enzymes, cortical neurons were collected from the samples. Then, the morphology of the cortical neurons was determined. Moreover, the cortical neurons were transfected with the negative control (NC) lentivirus. The transfection efficiency and morphology were determined and compared. Compared with the papain group, cortical neurons in the trypsin group were more in number, had larger cell size, had longer axonal length, and had fewer impurities. The transfection efficiency of the trypsin group (57.77%) was higher than that of the papain group (53.83%). The morphology of neurons that was displayed showed that the cell body of most neurons shrank and became smaller, and the axis mutation became shorter and less in the papain group 6 days after transfection with the NC lentivirus. Trypsin is more efficient in digesting neurons because the neurons digested by this enzyme are more in number, have a larger cell body, longer axons, and greater transfection efficiency.

Efficacy of the lumbar sympathetic ganglion block in lower limb pain and its application prospects during the perioperative period.

The sympathetic nervous system is involved in the physiological pathogenesis of many different types of chronic pain. Sympathetic blocks can interrupt the reflex control system by intercepting the noxious afferent fibers accompanying autonomic nerves, resulting in changes in peripheral or central sensory processing. A lumbar sympathetic ganglion block (LSGB), as a treatment method, refers to the injection of nerve blockers into the corresponding lumbar sympathetic nerve segments, usually requiring imaging assistance (CT, X-ray, ultrasound) to guide. At present, LSGB has been widely used in the clinical treatment of lower limb pain, such as neuropathic pain, lower limb ischemic pain, and so on. Its mechanism of action may be through inhibiting sympathetic nerve activity and dilating blood vessels, thereby alleviating pain and inhibiting stress response. However, there are few reports of LSGB during the perioperative period, especially in postoperative pain and gastrointestinal function. Therefore, by studying the literature about LSGB-related studies, this article reviews the anatomy of the lumbar sympathetic nerve (LSN), with its clinical application and possible mechanism. We reviewed the analgesic effect of LSGB in patients with lower limb pain and postoperative pain and the potential application prospects in the recovery of gastrointestinal function, finally providing a reference for its clinical application.

A systematic review and meta-analysis on the curative effects of cardiothoracic surgery for critical patients in the intensive care unit.

BACKGROUND: The aim of this study was to explore the curative effects of cardiothoracic surgery (CTS) for critical patients in the intensive care unit (ICU) using meta-analysis. METHODS: Literature was searched using the following search terms: "cardiothoracic surgery", "intensive care unit", "critical patients", "post-operation", and "curative effects". Rev Man 5.3 was used for meta-analysis. RESULTS: A total of 15 randomized controlled trials (RCTs) were included, all of which had a low risk of bias, indicating medium and high quality. At 30 days after CTS, the number of patients with grade III and IV cardiac function was reduced by 76.84%, and the overall heterogeneity test results revealed that Tau2=0.09, Chi2=17.08, df=5, I2=71%, P=0.004<0.01, Z=7.62, RR =0.33, and 95% CI: 0.24 to 0.43. The incidence of adverse reactions was analyzed in 6 RCTs, and mainly manifested as improper anticoagulation thrombosis and bleeding. The overall heterogeneity test results revealed that Chi2=1.07, df=5, I2=0%, P=0.96, Z=4.93, OR =0.46, 95% CI: 0.34 to 0.63, and P<0.01. The 30-day mortality rate was analyzed in 8 RCTs. The overall analysis using the fixed effects model revealed that there was a notable difference between the experimental group and the baseline, with Z=10.11, OR =0.12, 95% CI: 0.08 to 0.18, and P<0.01. DISCUSSION: CTS can reduce the incidence of adverse events and the mortality rate of critical patients in the ICU, demonstrating high safety.

Pathogens distribution and antimicrobial resistance in bloodstream infections in twenty-five neonatal intensive care units in China, 2017-2019.

BACKGROUND: Overcrowding, abuse of antibiotics and increasing antimicrobial resistance negatively affect neonatal survival rates in developing countries. We aimed to define pathogens and their antimicrobial resistance (AMR) of early-onset sepsis (EOS), hospital-acquired late-onset sepsis (HALOS) and community-acquired late-onset sepsis (CALOS) in 25 neonatal intensive care units (NICUs) in China. STUDY DESIGN: This retrospective descriptive study included pathogens and their AMR from all neonates with bloodstream infections (BSIs) admitted to 25 tertiary hospitals in China from January 1, 2017, and December 31, 2019. We defined EOS as the occurrence of BSI at or before 72 h of life and late-onset sepsis (LOS) if BSI occurred after 72 h of life. LOS were classified as CALOS if occurrence of BSI was ≤ 48 h after admission, and HALOS, if occurrence was > 48 h after admission. RESULTS: We identified 1092 pathogens of BSIs in 1088 infants from 25 NICUs. Thirty-two percent of all pathogens were responsible for EOS, 64.3% HALOS, and 3.7% CALOS. Gram-negative (GN) bacteria accounted for a majority of pathogens in EOS (56.7%) and HALOS (62.2%). The most frequent pathogens causing EOS were Escherichia coli (27.2%) and group B streptococcus (GBS; 14.6%) whereas in CALOS they were GBS (46.3%) and Staphylococcus aureus (41.5%). Klebsiella pneumoniae (27.9%), Escherichia coli (15.7%) and Fungi (12.8%) were the top three isolates in HALOS. Third-generation cephalosporin resistance rates in GN bacteria ranged from 9.7 to 55.6% in EOS and 26% to 63.3% in HALOS. Carbapenem resistance rates in GN bacteria ranged from 2.7 to 31.3% in HALOS and only six isolates in EOS were carbapenem resistant. High rates of multidrug resistance were observed in Klebsiella pneumoniae (60.7%) in HALOS and in Escherichia coli (44.4%) in EOS. All gram-positive bacteria were susceptible to vancomycin except for three Enterococcus faecalis in HALOS. All-cause mortality was higher among neonates with EOS than HALOS (7.4% VS 4.4%, [OR] 0.577, 95% CI 0.337-0.989; P = 0.045). CONCLUSIONS: Escherichia coli, Klebsiella pneumoniae and GBS were the leading pathogens in EOS, HALOS and CALOS, respectively. The high proportion of pathogens and high degree of antimicrobial resistance in HALOS underscore understanding of the pathogenesis and emphasise the need to devise effective interventions in developing countries.

Association between admission hypothermia and outcomes in very low birth weight infants in China: a multicentre prospective study.

BACKGROUND: The objective of this prospective, multicentre, observational cohort study was to evaluate the association between admission hypothermia and neonatal outcomes in very low-birth weight (VLBW) infants in multiple neonatal intensive care units (NICUs) in China. METHODS: Since January 1, 2018, a neonatal homogeneous cooperative research platform-Shandong Neonatal Network (SNN) has been established. The platform collects clinical data in a prospective manner on preterm infants with birth weights (BWs) < 1500 g and gestational ages (GAs) < 34 weeks born in 28 NICUs in Shandong Province. These infants were divided into normothermia, mild or moderate/severe hypothermia groups according to the World Health Organization (WHO) classifications of hypothermia. Associations between outcomes and hypothermia were tested in a bivariate analysis, followed by a logistic regression analysis. RESULTS: A total of 1247 VLBW infants were included in this analysis, of which 1100 infants (88.2%) were included in the hypothermia group, 554 infants (44.4%) in the mild hypothermia group and 546 infants (43.8%) in the moderate/severe hypothermia group. Small for gestational age (SGA), caesarean section, a low Apgar score at 5 min and intubation in the delivery room (DR) were related to admission hypothermia (AH). Mortality was the lowest when their admission temperature was 36.5 ~ 37.5 °C, and after adjustment for maternal and infant characteristics, mortality was significantly associated with AH. Compared with infants with normothermia (36.5 ~ 37.5 °C), the adjusted ORs of all deaths increased to 4.148 (95% CI 1.505-11.437) and 1.806 (95% CI 0.651-5.009) for infants with moderate/severe hypothermia and mild hypothermia, respectively. AH was also associated with a high likelihood of respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH), and late-onset neonatal sepsis (LOS). CONCLUSIONS: AH is still very high in VLBW infants in NICUs in China. SGA, caesarean section, a low Apgar score at 5 min and intubation in the DR were associated with increased odds of hypothermia. Moderate/severe hypothermia was associated with mortality and poor outcomes, such as RDS, IVH, LOS.

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering.

Terpenoids are the largest and structurally most diverse class of natural products. They possess potent and specific biological activity in multiple assays and against diseases, including cancer and malaria as notable examples. Although the number of characterized terpenoid molecules is huge, our knowledge of how they are biosynthesized is limited, particularly when compared to the well-studied thiotemplate assembly lines. Bacteria have only recently been recognized as having the genetic potential to biosynthesize a large number of complex terpenoids, but our current ability to associate genetic potential with molecular structure is severely restricted. The canonical terpene biosynthetic pathway uses a single enzyme to form a cyclized hydrocarbon backbone followed by modifications with a suite of tailoring enzymes that can generate dozens of different products from a single backbone. This functional promiscuity of terpene biosynthetic pathways renders terpene biosynthesis susceptible to rational pathway engineering using the latest developments in the field of synthetic biology. These engineered pathways will not only facilitate the rational creation of both known and novel terpenoids, their development will deepen our understanding of a significant branch of biosynthesis. The biosynthetic insights gained will likely empower a greater degree of engineering proficiency for non-natural terpene biosynthetic pathways and pave the way towards the biotechnological production of high value terpenoids.

Factors associated with appendicular skeletal muscle mass among male Chinese patients with stable chronic obstructive pulmonary disease: A hospital-based cross-sectional study.

Limbs muscle wasting is a common disorder in patients with chronic obstructive pulmonary disease (COPD) that limits daily activities and exercise intolerance, especially in males. The present study aimed to estimate the prevalence of appendicular skeletal muscle mass (ASM) in male patients with stable COPD. In addition, factors associated with parameters of ASM were also investigated.We recruited 116 male patients with stable COPD from the outpatient clinic between September 2016 and December 2017. For each patient, we obtained demographic characteristics and measured post-bronchodilator forced expiratory volume in 1 second, symptoms, exacerbations history, and ASM. ASM was defined as the sum of the muscle masses of the 4 limbs.Appendicular skeletal muscle mass index (ASMI) in male patients with stable COPD was 8.2 ±â€Š0.9 kg/m, and the prevalence of low skeletal muscle mass was 7.8% (9 of 116 patients). Multiple linear-regression analysis showed that body mass index, occupation, fat-free mass index, and the modified medical research council scale were significantly correlated with ASMI. Compared with nonexercise group, lower limb muscle mass and ASM were significantly improved in physical exercise group.Underweight, retirement, fat-free mass depletion, and severe dyspnea are all risk factors for ASM in male patients with stable COPD. Our findings also justify the importance of exercise training in improving ASM.